--- /dev/null
+/* Last changed Time-stamp: <2007-05-09 16:11:21 ivo> */
+/*
+ partiton function for RNA secondary structures
+
+ Ivo L Hofacker
+ Stephan Bernhart
+ Vienna RNA package
+*/
+/*
+ $Log: part_func_co.c,v $
+ Revision 1.10 2007/05/10 17:27:01 ivo
+ make sure the relative error eps is positive in newton iteration
+
+ Revision 1.9 2006/05/10 15:12:11 ivo
+ some compiler choked on double semicolon after declaration
+
+ Revision 1.8 2006/04/05 12:52:31 ivo
+ Fix performance bug (O(n^4) loop)
+
+ Revision 1.7 2006/01/19 11:30:04 ivo
+ compute_probabilities should only look at one dimer at a time
+
+ Revision 1.6 2006/01/18 12:55:40 ivo
+ major cleanup of berni code
+ fix bugs related to confusing which free energy is returned by co_pf_fold()
+
+ Revision 1.5 2006/01/16 11:32:25 ivo
+ small bug in multiloop pair probs
+
+ Revision 1.4 2006/01/05 18:13:40 ivo
+ update
+
+ Revision 1.3 2006/01/04 15:14:29 ivo
+ fix bug in concentration calculations
+
+ Revision 1.2 2004/12/23 12:14:41 berni
+ *** empty log message ***
+
+ Revision 1.1 2004/12/22 10:46:17 berni
+
+ Partition function Cofolding 0.9, Computation of concentrations.
+
+ Revision 1.16 2003/08/04 09:14:09 ivo
+ finish up stochastic backtracking
+
+ Revision 1.15 2002/03/19 16:51:12 ivo
+ more on stochastic backtracking (still incomplete)
+
+ Revision 1.13 2001/11/16 17:30:04 ivo
+ add stochastic backtracking (still incomplete)
+*/
+
+#include <config.h>
+#include <stdio.h>
+#include <stdlib.h>
+#include <string.h>
+#include <math.h>
+#include <float.h> /* #defines FLT_MAX ... */
+#include <limits.h>
+
+#include "utils.h"
+#include "energy_par.h"
+#include "fold_vars.h"
+#include "pair_mat.h"
+#include "PS_dot.h"
+#include "params.h"
+#include "loop_energies.h"
+#include "part_func.h"
+#include "part_func_co.h"
+
+#ifdef _OPENMP
+#include <omp.h>
+#endif
+
+
+/*@unused@*/
+PRIVATE char rcsid[] UNUSED = "$Id: part_func_co.c,v 1.10 2007/05/10 17:27:01 ivo Exp $";
+
+#define ISOLATED 256.0
+#undef TURN
+#define TURN 0
+#define SAME_STRAND(I,J) (((I)>=cut_point)||((J)<cut_point))
+
+/* #define SAME_STRAND(I,J) (((J)<cut_point)||((I)>=cut_point2)||(((I)>=cut_point)&&((J)<cut_point2)))
+ */
+
+/*
+#################################
+# GLOBAL VARIABLES #
+#################################
+*/
+int mirnatog = 0;
+double F_monomer[2] = {0,0}; /* free energies of the two monomers */
+
+/*
+#################################
+# PRIVATE VARIABLES #
+#################################
+*/
+PRIVATE FLT_OR_DBL *expMLbase=NULL;
+PRIVATE FLT_OR_DBL *q=NULL, *qb=NULL, *qm=NULL, *qm1=NULL, *qqm=NULL, *qqm1=NULL, *qq=NULL, *qq1=NULL;
+PRIVATE FLT_OR_DBL *prml=NULL, *prm_l=NULL, *prm_l1=NULL, *q1k=NULL, *qln=NULL, *probs=NULL;
+PRIVATE FLT_OR_DBL *scale=NULL;
+PRIVATE pf_paramT *pf_params = NULL;
+PRIVATE char *ptype=NULL; /* precomputed array of pair types */
+PRIVATE int *jindx=NULL;
+PRIVATE int *my_iindx=NULL;
+PRIVATE int init_length; /* length in last call to init_pf_fold() */
+PRIVATE int do_bppm = 1; /* do backtracking per default */
+PRIVATE short *S=NULL, *S1=NULL;
+PRIVATE char *pstruc=NULL;
+PRIVATE char *sequence=NULL;
+PRIVATE double alpha = 1.0;
+PRIVATE int struct_constrained = 0;
+
+#ifdef _OPENMP
+
+/* NOTE: all variables are assumed to be uninitialized if they are declared as threadprivate
+*/
+#pragma omp threadprivate(expMLbase, q, qb, qm, qm1, qqm, qqm1, qq, qq1, prml, prm_l, prm_l1, q1k, qln,\
+ scale, pf_params, ptype, jindx, my_iindx, init_length, S, S1, pstruc, sequence, probs, do_bppm, alpha, struct_constrained)
+
+#endif
+
+
+/*
+#################################
+# PRIVATE FUNCTION DECLARATIONS #
+#################################
+*/
+PRIVATE void init_partfunc_co(int length, pf_paramT *parameters);
+PRIVATE void pf_co(const char *sequence);
+PRIVATE void pf_co_bppm(const char *sequence, char *structure);
+PRIVATE double *Newton_Conc(double ZAB, double ZAA, double ZBB, double concA, double concB,double* ConcVec);
+PRIVATE void scale_pf_params(unsigned int length, pf_paramT *parameters);
+PRIVATE void get_arrays(unsigned int length);
+PRIVATE void make_ptypes(const short *S, const char *structure);
+PRIVATE void backtrack(int i, int j);
+
+
+/*
+#################################
+# BEGIN OF FUNCTION DEFINITIONS #
+#################################
+*/
+
+PRIVATE void init_partfunc_co(int length, pf_paramT *parameters){
+ if (length<1) nrerror("init_pf_fold: length must be greater 0");
+
+#ifdef _OPENMP
+/* Explicitly turn off dynamic threads */
+ omp_set_dynamic(0);
+ free_co_pf_arrays(); /* free previous allocation */
+#else
+ if (init_length>0) free_co_pf_arrays(); /* free previous allocation */
+#endif
+
+#ifdef SUN4
+ nonstandard_arithmetic();
+#else
+#ifdef HP9
+ fpsetfastmode(1);
+#endif
+#endif
+ make_pair_matrix();
+ get_arrays((unsigned) length);
+ scale_pf_params((unsigned) length, parameters);
+ init_length = length;
+}
+
+PRIVATE void get_arrays(unsigned int length){
+ unsigned int size;
+
+ if((length +1) >= (unsigned int)sqrt((double)INT_MAX))
+ nrerror("get_arrays@part_func_co.c: sequence length exceeds addressable range");
+
+ size = sizeof(FLT_OR_DBL) * ((length+1)*(length+2)/2);
+ q = (FLT_OR_DBL *) space(size);
+ qb = (FLT_OR_DBL *) space(size);
+ qm = (FLT_OR_DBL *) space(size);
+ probs = (FLT_OR_DBL *) space(size);
+ qm1 = (FLT_OR_DBL *) space(size);
+ q1k = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+1));
+ qln = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ qq = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ qq1 = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ qqm = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ qqm1 = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ prm_l = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ prm_l1 = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ prml = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+2));
+ expMLbase = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+1));
+ scale = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL)*(length+1));
+ ptype = (char *) space(sizeof(char)*((length+1)*(length+2)/2));
+ my_iindx = get_iindx(length);
+ iindx = get_iindx(length); /* for backward compatibility and Perl wrapper */
+ jindx = get_indx(length);
+}
+
+PUBLIC void free_co_pf_arrays(void){
+ if(q) free(q);
+ if(qb) free(qb);
+ if(qm) free(qm);
+ if(qm1) free(qm1);
+ if(ptype) free(ptype);
+ if(qq) free(qq);
+ if(qq1) free(qq1);
+ if(qqm) free(qqm);
+ if(qqm1) free(qqm1);
+ if(q1k) free(q1k);
+ if(qln) free(qln);
+ if(prm_l) free(prm_l);
+ if(prm_l1) free(prm_l1);
+ if(prml) free(prml);
+ if(probs) free(probs);
+ if(expMLbase) free(expMLbase);
+ if(scale) free(scale);
+ if(my_iindx) free(my_iindx);
+ if(iindx) free(iindx); /* for backward compatibility and Perl wrapper */
+ if(jindx) free(jindx);
+ if(S) free(S);
+ if(S1) free(S1);
+
+ init_length=0;
+ q = qb = qm = qm1 = qq = qq1 = qqm = qqm1 = q1k = qln = prm_l = prm_l1 = prml = expMLbase = scale = probs = NULL;
+ ptype = NULL;
+ S = S1 = NULL;
+ my_iindx = jindx = iindx = NULL;
+
+#ifdef SUN4
+ standard_arithmetic();
+#else
+#ifdef HP9
+ fpsetfastmode(0);
+#endif
+#endif
+}
+
+/*-----------------------------------------------------------------*/
+PUBLIC cofoldF co_pf_fold(char *sequence, char *structure){
+ return co_pf_fold_par(sequence, structure, NULL, do_backtrack, fold_constrained);
+}
+
+PUBLIC cofoldF co_pf_fold_par(char *sequence,
+ char *structure,
+ pf_paramT *parameters,
+ int calculate_bppm,
+ int is_constrained){
+
+ int n;
+ FLT_OR_DBL Q;
+ cofoldF X;
+ double free_energy;
+
+ n = (int) strlen(sequence);
+ do_bppm = calculate_bppm;
+ struct_constrained = is_constrained;
+
+#ifdef _OPENMP
+ /* always init everything since all global static variables are uninitialized when entering a thread */
+ init_partfunc_co(n, parameters);
+#else
+ if(parameters) init_partfunc_co(n, parameters);
+ else if (n > init_length) init_partfunc_co(n, parameters);
+ else if (fabs(pf_params->temperature - temperature)>1e-6) update_co_pf_params_par(n, parameters);
+#endif
+
+ /* printf("mirnatog=%d\n",mirnatog); */
+
+ if(S) free(S);
+ S = encode_sequence(sequence, 0);
+ if(S1) free(S1);
+ S1 = encode_sequence(sequence, 1);
+
+ make_ptypes(S, structure);
+
+ pf_co(sequence);
+
+ if (backtrack_type=='C') Q = qb[my_iindx[1]-n];
+ else if (backtrack_type=='M') Q = qm[my_iindx[1]-n];
+ else Q = q[my_iindx[1]-n];
+ /* ensemble free energy in Kcal/mol */
+ if (Q<=FLT_MIN) fprintf(stderr, "pf_scale too large\n");
+ free_energy = (-log(Q)-n*log(pf_params->pf_scale))*pf_params->kT/1000.0;
+ /* in case we abort because of floating point errors */
+ if (n>1600) fprintf(stderr, "free energy = %8.2f\n", free_energy);
+ /*probability of molecules being bound together*/
+
+
+ /*Computation of "real" Partition function*/
+ /*Need that for concentrations*/
+ if (cut_point>0){
+ double kT, pbound, QAB, QToT, Qzero;
+
+ kT = pf_params->kT/1000.0;
+ Qzero=q[my_iindx[1]-n];
+ QAB=(q[my_iindx[1]-n]-q[my_iindx[1]-(cut_point-1)]*q[my_iindx[cut_point]-n])*pf_params->expDuplexInit;
+ /*correction for symmetry*/
+ if((n-(cut_point-1)*2)==0) {
+ if ((strncmp(sequence, sequence+cut_point-1, cut_point-1))==0) {
+ QAB/=2;
+ }}
+
+ QToT=q[my_iindx[1]-(cut_point-1)]*q[my_iindx[cut_point]-n]+QAB;
+ pbound=1-(q[my_iindx[1]-(cut_point-1)]*q[my_iindx[cut_point]-n]/QToT);
+ X.FAB = -kT*(log(QToT)+n*log(pf_params->pf_scale));
+ X.F0AB = -kT*(log(Qzero)+n*log(pf_params->pf_scale));
+ X.FcAB = (QAB>1e-17) ? -kT*(log(QAB)+n*log(pf_params->pf_scale)) : 999;
+ X.FA = -kT*(log(q[my_iindx[1]-(cut_point-1)]) + (cut_point-1)*log(pf_params->pf_scale));
+ X.FB = -kT*(log(q[my_iindx[cut_point]-n]) + (n-cut_point+1)*log(pf_params->pf_scale));
+
+ /* printf("QAB=%.9f\tQtot=%.9f\n",QAB/scale[n],QToT/scale[n]);*/
+ }
+ else {
+ X.FA = X.FB = X.FAB = X.F0AB = free_energy;
+ X.FcAB = 0;
+ }
+
+ /* backtracking to construct binding probabilities of pairs*/
+ if(do_bppm){
+ pf_co_bppm(sequence, structure);
+ /*
+ * Backward compatibility:
+ * This block may be removed if deprecated functions
+ * relying on the global variable "pr" vanish from within the package!
+ */
+ pr = probs;
+ /*
+ {
+ if(pr) free(pr);
+ pr = (FLT_OR_DBL *) space(sizeof(FLT_OR_DBL) * ((n+1)*(n+2)/2));
+ memcpy(pr, probs, sizeof(FLT_OR_DBL) * ((n+1)*(n+2)/2));
+ }
+ */
+ }
+ return X;
+}
+
+/* forward recursion of pf cofolding */
+PRIVATE void pf_co(const char *sequence){
+ int n, i,j,k,l, ij, u,u1,ii, type, type_2, tt;
+ FLT_OR_DBL temp, Qmax=0;
+ FLT_OR_DBL qbt1, *tmp;
+ FLT_OR_DBL expMLclosing;
+ double max_real;
+ int noGUclosure = pf_params->model_details.noGUclosure;
+
+ max_real = (sizeof(FLT_OR_DBL) == sizeof(float)) ? FLT_MAX : DBL_MAX;
+ n = (int) strlen(sequence);
+
+ expMLclosing = pf_params->expMLclosing;
+
+
+ /*array initialization ; qb,qm,q
+ qb,qm,q (i,j) are stored as ((n+1-i)*(n-i) div 2 + n+1-j */
+
+ /* for (d=0; d<=TURN; d++) */
+ for (i=1; i<=n/*-d*/; i++) {
+ ij = my_iindx[i]-i;
+ q[ij]=scale[1];
+ qb[ij]=qm[ij]=0.0;
+ }
+
+ for (i=0; i<=n; i++)
+ qq[i]=qq1[i]=qqm[i]=qqm1[i]=prm_l[i]=prm_l1[i]=prml[i]=0;
+
+ for (j=TURN+2;j<=n; j++) {
+ for (i=j-TURN-1; i>=1; i--) {
+ /* construction of partition function of segment i,j*/
+ /*firstly that given i bound to j : qb(i,j) */
+ u = j-i-1; ij = my_iindx[i]-j;
+ type = ptype[ij];
+ qbt1=0;
+ if (type!=0) {
+ /*hairpin contribution*/
+ if SAME_STRAND(i,j){
+ if (((type==3)||(type==4))&&noGUclosure) qbt1 = 0;
+ else
+ qbt1 = exp_E_Hairpin(u, type, S1[i+1], S1[j-1], sequence+i-1, pf_params)*scale[u+2];
+
+ }
+
+ /* interior loops with interior pair k,l */
+ for (k=i+1; k<=MIN2(i+MAXLOOP+1,j-TURN-2); k++) {
+ u1 = k-i-1;
+ for (l=MAX2(k+TURN+1,j-1-MAXLOOP+u1); l<j; l++) {
+ if ((SAME_STRAND(i,k))&&(SAME_STRAND(l,j))){
+ type_2 = ptype[my_iindx[k]-l];
+ if (type_2) {
+ type_2 = rtype[type_2];
+ qbt1 += qb[my_iindx[k]-l] *
+ exp_E_IntLoop(u1, j-l-1, type, type_2,
+ S1[i+1], S1[j-1], S1[k-1], S1[l+1], pf_params)*scale[u1+j-l+1];
+ }
+ }
+ }
+ }
+ /*multiple stem loop contribution*/
+ ii = my_iindx[i+1]; /* ii-k=[i+1,k-1] */
+ temp = 0.0;
+ if (SAME_STRAND(i,i+1) && SAME_STRAND(j-1,j)) {
+ for (k=i+2; k<=j-1; k++) {
+ if (SAME_STRAND(k-1,k))
+ temp += qm[ii-(k-1)]*qqm1[k];
+ }
+ tt = rtype[type];
+ temp*=exp_E_MLstem(tt, S1[j-1], S1[i+1], pf_params)*scale[2];
+ temp*=expMLclosing;
+ qbt1 += temp;
+ }
+ /*qc contribution*/
+ temp=0.0;
+ if (!SAME_STRAND(i,j)){
+ tt = rtype[type];
+ temp=q[my_iindx[i+1]-(cut_point-1)]*q[my_iindx[cut_point]-(j-1)];
+ if ((j==cut_point)&&(i==cut_point-1)) temp=scale[2];
+ else if (i==cut_point-1) temp=q[my_iindx[cut_point]-(j-1)]*scale[1];
+ else if (j==cut_point) temp=q[my_iindx[i+1]-(cut_point-1)]*scale[1];
+ if (j>cut_point) temp*=scale[1];
+ if (i<cut_point-1) temp*=scale[1];
+ temp *= exp_E_ExtLoop(tt, SAME_STRAND(j-1,j) ? S1[j-1] : -1, SAME_STRAND(i,i+1) ? S1[i+1] : -1, pf_params);
+ qbt1+=temp;
+ }
+ qb[ij] = qbt1;
+ } /* end if (type!=0) */
+ else qb[ij] = 0.0;
+ /* construction of qqm matrix containing final stem
+ contributions to multiple loop partition function
+ from segment i,j */
+ if (SAME_STRAND(j-1,j)) {
+ qqm[i] = qqm1[i]*expMLbase[1];
+ }
+ else qqm[i]=0;
+ if (type&&SAME_STRAND(i-1,i)&&SAME_STRAND(j,j+1)) {
+ qbt1 = qb[ij];
+ qbt1 *= exp_E_MLstem(type, (i>1) ? S1[i-1] : -1, (j<n) ? S1[j+1] : -1, pf_params);
+ qqm[i] += qbt1;
+ }
+
+ if (qm1) qm1[jindx[j]+i] = qqm[i]; /* for stochastic backtracking */
+
+
+ /*construction of qm matrix containing multiple loop
+ partition function contributions from segment i,j */
+ temp = 0.0;
+ ii = my_iindx[i]; /* ii-k=[i,k] */
+
+ for (k=i+1; k<=j; k++) {
+ if (SAME_STRAND(k-1,k)) temp += (qm[ii-(k-1)])*qqm[k];
+ if (SAME_STRAND(i,k)) temp += expMLbase[k-i]*qqm[k];
+
+ }
+
+ qm[ij] = (temp + qqm[i]);
+
+ /*auxiliary matrix qq for cubic order q calculation below */
+ qbt1 = qb[ij];
+ if (type) {
+ qbt1 *= exp_E_ExtLoop(type, ((i>1)&&(SAME_STRAND(i-1,i))) ? S1[i-1] : -1, ((j<n)&&(SAME_STRAND(j,j+1))) ? S1[j+1] : -1, pf_params);
+ }
+ qq[i] = qq1[i]*scale[1] + qbt1;
+ /*construction of partition function for segment i,j */
+ temp = 1.0*scale[1+j-i] + qq[i];
+ for (k=i; k<=j-1; k++) temp += q[ii-k]*qq[k+1];
+ q[ij] = temp;
+
+ if (temp>Qmax) {
+ Qmax = temp;
+ if (Qmax>max_real/10.)
+ fprintf(stderr, "Q close to overflow: %d %d %g\n", i,j,temp);
+ }
+ if (temp>=max_real) {
+ PRIVATE char msg[128];
+ snprintf(msg, 127, "overflow in co_pf_fold while calculating q[%d,%d]\n"
+ "use larger pf_scale", i,j);
+ nrerror(msg);
+ }
+ }
+ tmp = qq1; qq1 =qq; qq =tmp;
+ tmp = qqm1; qqm1=qqm; qqm=tmp;
+ }
+}
+
+/* backward recursion of pf cofolding */
+PRIVATE void pf_co_bppm(const char *sequence, char *structure){
+ int n, i,j,k,l, ij, kl, ii, ll, type, type_2, tt, ov=0;
+ FLT_OR_DBL temp, Qmax=0, prm_MLb;
+ FLT_OR_DBL prmt,prmt1;
+ FLT_OR_DBL *tmp;
+ FLT_OR_DBL expMLclosing;
+ double max_real;
+
+ max_real = (sizeof(FLT_OR_DBL) == sizeof(float)) ? FLT_MAX : DBL_MAX;
+ n = (int) strlen(sequence);
+
+ expMLclosing = pf_params->expMLclosing;
+
+ /* backtracking to construct binding probabilities of pairs*/
+ if ((S != NULL) && (S1 != NULL)) {
+ FLT_OR_DBL *Qlout, *Qrout;
+ Qmax=0;
+ Qrout=(FLT_OR_DBL *)space(sizeof(FLT_OR_DBL) * (n+2));
+ Qlout=(FLT_OR_DBL *)space(sizeof(FLT_OR_DBL) * (cut_point+2));
+
+ for (k=1; k<=n; k++) {
+ q1k[k] = q[my_iindx[1] - k];
+ qln[k] = q[my_iindx[k] -n];
+ }
+ q1k[0] = 1.0;
+ qln[n+1] = 1.0;
+
+ /* pr = q; / * recycling */
+
+ /* 1. exterior pair i,j and initialization of pr array */
+ for (i=1; i<=n; i++) {
+ for (j=i; j<=MIN2(i+TURN,n); j++) probs[my_iindx[i]-j] = 0;
+ for (j=i+TURN+1; j<=n; j++) {
+ ij = my_iindx[i]-j;
+ type = ptype[ij];
+ if (type&&(qb[ij]>0.)) {
+ probs[ij] = q1k[i-1]*qln[j+1]/q1k[n];
+ probs[ij] *= exp_E_ExtLoop(type, ((i>1)&&(SAME_STRAND(i-1,i))) ? S1[i-1] : -1, ((j<n)&&(SAME_STRAND(j,j+1))) ? S1[j+1] : -1, pf_params);
+ } else
+ probs[ij] = 0;
+ }
+ }
+
+ for (l=n; l>TURN+1; l--) {
+
+ /* 2. bonding k,l as substem of 2:loop enclosed by i,j */
+ for (k=1; k<l-TURN; k++) {
+ kl = my_iindx[k]-l;
+ type_2 = ptype[kl]; type_2 = rtype[type_2];
+ if (qb[kl]==0) continue;
+
+ for (i=MAX2(1,k-MAXLOOP-1); i<=k-1; i++)
+ for (j=l+1; j<=MIN2(l+ MAXLOOP -k+i+2,n); j++) {
+ if ((SAME_STRAND(i,k))&&(SAME_STRAND(l,j))){
+ ij = my_iindx[i] - j;
+ type = ptype[ij];
+ if ((probs[ij]>0)) {
+ probs[kl] += probs[ij]*exp_E_IntLoop(k-i-1, j-l-1, type, type_2,
+ S1[i+1], S1[j-1], S1[k-1], S1[l+1], pf_params)*scale[k-i+j-l];
+ }
+ }
+ }
+ }
+ /* 3. bonding k,l as substem of multi-loop enclosed by i,j */
+ prm_MLb = 0.;
+ if ((l<n)&&(SAME_STRAND(l,l+1)))
+ for (k=2; k<l-TURN; k++) {
+ i = k-1;
+ prmt = prmt1 = 0.0;
+
+ ii = my_iindx[i]; /* ii-j=[i,j] */
+ ll = my_iindx[l+1]; /* ll-j=[l+1,j] */
+ tt = ptype[ii-(l+1)]; tt=rtype[tt];
+ if (SAME_STRAND(i,k)){
+ prmt1 = probs[ii-(l+1)]*expMLclosing;
+ prmt1 *= exp_E_MLstem(tt, S1[l], S1[i+1], pf_params);
+ for (j=l+2; j<=n; j++) {
+ if (SAME_STRAND(j-1,j)){ /*??*/
+ tt = ptype[ii-j]; tt = rtype[tt];
+ prmt += probs[ii-j]*exp_E_MLstem(tt, S1[j-1], S1[i+1], pf_params)*qm[ll-(j-1)];
+ }
+ }
+ }
+ kl = my_iindx[k]-l;
+ tt = ptype[kl];
+ prmt *= expMLclosing;
+ prml[ i] = prmt;
+ prm_l[i] = prm_l1[i]*expMLbase[1]+prmt1;
+
+ prm_MLb = prm_MLb*expMLbase[1] + prml[i];
+ /* same as: prm_MLb = 0;
+ for (i=1; i<=k-1; i++) prm_MLb += prml[i]*expMLbase[k-i-1]; */
+
+ prml[i] = prml[ i] + prm_l[i];
+
+ if (qb[kl] == 0.) continue;
+
+ temp = prm_MLb;
+
+ for (i=1;i<=k-2; i++) {
+ if ((SAME_STRAND(i,i+1))&&(SAME_STRAND(k-1,k))){
+ temp += prml[i]*qm[my_iindx[i+1] - (k-1)];
+ }
+ }
+ temp *= exp_E_MLstem( tt,
+ ((k>1)&&SAME_STRAND(k-1,k)) ? S1[k-1] : -1,
+ ((l<n)&&SAME_STRAND(l,l+1)) ? S1[l+1] : -1,
+ pf_params) * scale[2];
+ probs[kl] += temp;
+
+ if (probs[kl]>Qmax) {
+ Qmax = probs[kl];
+ if (Qmax>max_real/10.)
+ fprintf(stderr, "P close to overflow: %d %d %g %g\n",
+ i, j, probs[kl], qb[kl]);
+ }
+ if (probs[kl]>=max_real) {
+ ov++;
+ probs[kl]=FLT_MAX;
+ }
+
+ } /* end for (k=..) multloop*/
+ else /* set prm_l to 0 to get prm_l1 to be 0 */
+ for (i=0; i<=n; i++) prm_l[i]=0;
+
+ tmp = prm_l1; prm_l1=prm_l; prm_l=tmp;
+ /*computation of .(..(...)..&..). type features?*/
+ if (cut_point<=0) continue; /* no .(..(...)..&..). type features*/
+ if ((l==n)||(l<=2)) continue; /* no .(..(...)..&..). type features*/
+ /*new version with O(n^3)??*/
+ if (l>cut_point) {
+ if (l<n) {
+ int t,kt;
+ for (t=n; t>l; t--) {
+ for (k=1; k<cut_point; k++) {
+ kt=my_iindx[k]-t;
+ type=rtype[ptype[kt]];
+ temp = probs[kt] * exp_E_ExtLoop(type, S1[t-1], (SAME_STRAND(k,k+1)) ? S1[k+1] : -1, pf_params) * scale[2];
+ if (l+1<t) temp*=q[my_iindx[l+1]-(t-1)];
+ if (SAME_STRAND(k,k+1)) temp*=q[my_iindx[k+1]-(cut_point-1)];
+ Qrout[l]+=temp;
+ }
+ }
+ }
+ for (k=l-1; k>=cut_point; k--) {
+ if (qb[my_iindx[k]-l]) {
+ kl=my_iindx[k]-l;
+ type=ptype[kl];
+ temp = Qrout[l];
+ temp *= exp_E_ExtLoop(type, (k>cut_point) ? S1[k-1] : -1, (l < n) ? S1[l+1] : -1, pf_params);
+ if (k>cut_point) temp*=q[my_iindx[cut_point]-(k-1)];
+ probs[kl]+=temp;
+ }
+ }
+ }
+ else if (l==cut_point ) {
+ int t, sk,s;
+ for (t=2; t<cut_point;t++) {
+ for (s=1; s<t; s++) {
+ for (k=cut_point; k<=n; k++) {
+ sk=my_iindx[s]-k;
+ if (qb[sk]) {
+ type=rtype[ptype[sk]];
+ temp=probs[sk]*exp_E_ExtLoop(type, (SAME_STRAND(k-1,k)) ? S1[k-1] : -1, S1[s+1], pf_params)*scale[2];
+ if (s+1<t) temp*=q[my_iindx[s+1]-(t-1)];
+ if (SAME_STRAND(k-1,k)) temp*=q[my_iindx[cut_point]-(k-1)];
+ Qlout[t]+=temp;
+ }
+ }
+ }
+ }
+ }
+ else if (l<cut_point) {
+ for (k=1; k<l; k++) {
+ if (qb[my_iindx[k]-l]) {
+ type=ptype[my_iindx[k]-l];
+ temp=Qlout[k];
+ temp *= exp_E_ExtLoop(type, (k>1) ? S1[k-1] : -1, (l<(cut_point-1)) ? S1[l+1] : -1, pf_params);
+ if (l+1<cut_point) temp*=q[my_iindx[l+1]-(cut_point-1)];
+ probs[my_iindx[k]-l]+=temp;
+ }
+ }
+ }
+ } /* end for (l=..) */
+ free(Qlout);
+ free(Qrout);
+ for (i=1; i<=n; i++)
+ for (j=i+TURN+1; j<=n; j++) {
+ ij = my_iindx[i]-j;
+ probs[ij] *= qb[ij];
+ }
+
+ if (structure!=NULL)
+ bppm_to_structure(structure, probs, n);
+ } /* end if (do_backtrack)*/
+
+ if (ov>0) fprintf(stderr, "%d overflows occurred while backtracking;\n"
+ "you might try a smaller pf_scale than %g\n",
+ ov, pf_params->pf_scale);
+}
+
+
+PRIVATE void scale_pf_params(unsigned int length, pf_paramT *parameters){
+ unsigned int i;
+ double kT, scaling_factor;
+
+ if(pf_params) free(pf_params);
+
+ if(parameters){
+ pf_params = get_boltzmann_factor_copy(parameters);
+ } else {
+ model_detailsT md;
+ set_model_details(&md);
+ pf_params = get_boltzmann_factors(temperature, alpha, md, pf_scale);
+ }
+
+ scaling_factor = pf_params->pf_scale;
+ kT = pf_params->kT; /* kT in cal/mol */
+
+ /* scaling factors (to avoid overflows) */
+ if (scaling_factor == -1) { /* mean energy for random sequences: 184.3*length cal */
+ scaling_factor = exp(-(-185+(pf_params->temperature-37.)*7.27)/kT);
+ if (scaling_factor<1) scaling_factor=1;
+ pf_params->pf_scale = scaling_factor;
+ }
+ scale[0] = 1.;
+ scale[1] = 1./scaling_factor;
+ expMLbase[0] = 1;
+ expMLbase[1] = pf_params->expMLbase/scaling_factor;
+ for (i=2; i<=length; i++) {
+ scale[i] = scale[i/2]*scale[i-(i/2)];
+ expMLbase[i] = pow(pf_params->expMLbase, (double)i) * scale[i];
+ }
+}
+
+/*----------------------------------------------------------------------*/
+
+/*----------------------------------------------------------------------*/
+
+/*---------------------------------------------------------------------------*/
+
+PUBLIC void update_co_pf_params(int length){
+ update_co_pf_params_par(length, NULL);
+}
+
+PUBLIC void update_co_pf_params_par(int length, pf_paramT *parameters){
+ make_pair_matrix();
+ scale_pf_params((unsigned) length, parameters);
+}
+
+/*---------------------------------------------------------------------------*/
+PRIVATE void make_ptypes(const short *S, const char *structure) {
+ int n,i,j,k,l;
+ int noLP = pf_params->model_details.noLP;
+
+ n=S[0];
+ for (k=1; k<=n-TURN-1; k++)
+ for (l=1; l<=2; l++) {
+ int type,ntype=0,otype=0;
+ i=k; j = i+TURN+l;
+ if (j>n) continue;
+ type = pair[S[i]][S[j]];
+ while ((i>=1)&&(j<=n)) {
+ if ((i>1)&&(j<n)) ntype = pair[S[i-1]][S[j+1]];
+ if (noLP && (!otype) && (!ntype))
+ type = 0; /* i.j can only form isolated pairs */
+ qb[my_iindx[i]-j] = 0.;
+ ptype[my_iindx[i]-j] = (char) type;
+ otype = type;
+ type = ntype;
+ i--; j++;
+ }
+
+ }
+
+ if (struct_constrained&&(structure!=NULL)) {
+ constrain_ptypes(structure, (unsigned int)n, ptype, NULL, TURN, 1);
+ for(j=1; j<=n; j++) {
+ switch (structure[j-1]) {
+ case 'l': /*only intramolecular basepairing*/
+ if (j<cut_point) for (l=cut_point; l<=n; l++) ptype[my_iindx[j]-l] = 0;
+ else for (l=1; l<cut_point; l++) ptype[my_iindx[l]-j] =0;
+ break;
+ case 'e': /*only intermolecular bp*/
+ if (j<cut_point) {
+ for (l=1; l<j; l++) ptype[my_iindx[l]-j] =0;
+ for (l=j+1; l<cut_point; l++) ptype[my_iindx[j]-l] = 0;
+ }
+ else {
+ for (l=cut_point; l<j; l++) ptype[my_iindx[l]-j] =0;
+ for (l=j+1; l<=n; l++) ptype[my_iindx[j]-l] = 0;
+ }
+ break;
+ }
+ }
+ }
+ if (mirnatog==1) { /*microRNA toggle: no intramolec. bp in 2. molec*/
+ for (j=cut_point; j<n; j++) {
+ for (l=j+1; l<=n; l++) {
+ ptype[my_iindx[j]-l] = 0;
+ }
+ }
+ }
+}
+
+/*
+ stochastic backtracking in pf_fold arrays
+ returns random structure S with Boltzman probabilty
+ p(S) = exp(-E(S)/kT)/Z
+*/
+PRIVATE void backtrack_qm1(int i,int j) {
+ /* i is paired to l, i<l<j; backtrack in qm1 to find l */
+ int ii, l, type;
+ double qt, r;
+ r = urn() * qm1[jindx[j]+i];
+ ii = my_iindx[i];
+ for (qt=0., l=i+TURN+1; l<=j; l++) {
+ type = ptype[ii-l];
+ if (type)
+ qt += qb[ii-l]*exp_E_MLstem(type, S1[i-1], S1[l+1], pf_params) * expMLbase[j-l];
+ if (qt>=r) break;
+ }
+ if (l>j) nrerror("backtrack failed in qm1");
+ backtrack(i,l);
+}
+
+PRIVATE void backtrack(int i, int j) {
+ int noGUclosure = pf_params->model_details.noGUclosure;
+
+ do {
+ double r, qbt1;
+ int k, l, type, u, u1;
+
+ pstruc[i-1] = '('; pstruc[j-1] = ')';
+
+ r = urn() * qb[my_iindx[i]-j];
+ type = ptype[my_iindx[i]-j];
+ u = j-i-1;
+ /*hairpin contribution*/
+ if (((type==3)||(type==4))&&noGUclosure) qbt1 = 0;
+ else
+ qbt1 = exp_E_Hairpin(u, type, S1[i+1], S1[j-1], sequence+i-1, pf_params)*scale[u+2];
+
+ if (qbt1>r) return; /* found the hairpin we're done */
+
+ for (k=i+1; k<=MIN2(i+MAXLOOP+1,j-TURN-2); k++) {
+ u1 = k-i-1;
+ for (l=MAX2(k+TURN+1,j-1-MAXLOOP+u1); l<j; l++) {
+ int type_2;
+ type_2 = ptype[my_iindx[k]-l];
+ if (type_2) {
+ type_2 = rtype[type_2];
+ qbt1 += qb[my_iindx[k]-l] *
+ exp_E_IntLoop(u1, j-l-1, type, type_2,
+ S1[i+1], S1[j-1], S1[k-1], S1[l+1], pf_params)*scale[u1+j-l+1];
+ }
+ if (qbt1 > r) break;
+ }
+ if (qbt1 > r) break;
+ }
+ if (l<j) {
+ i=k; j=l;
+ }
+ else break;
+ } while (1);
+
+ /* backtrack in multi-loop */
+ {
+ double r, qt;
+ int k, ii, jj;
+
+ i++; j--;
+ /* find the first split index */
+ ii = my_iindx[i]; /* ii-j=[i,j] */
+ jj = jindx[j]; /* jj+i=[j,i] */
+ for (qt=0., k=i+1; k<j; k++) qt += qm[ii-(k-1)]*qm1[jj+k];
+ r = urn() * qt;
+ for (qt=0., k=i+1; k<j; k++) {
+ qt += qm[ii-(k-1)]*qm1[jj+k];
+ if (qt>=r) break;
+ }
+ if (k>=j) nrerror("backtrack failed, can't find split index ");
+
+ backtrack_qm1(k, j);
+
+ j = k-1;
+ while (j>i) {
+ /* now backtrack [i ... j] in qm[] */
+ jj = jindx[j];
+ ii = my_iindx[i];
+ r = urn() * qm[ii - j];
+ qt = qm1[jj+i]; k=i;
+ if (qt<r)
+ for (k=i+1; k<=j; k++) {
+ qt += (qm[ii-(k-1)]+expMLbase[k-i])*qm1[jj+k];
+ if (qt >= r) break;
+ }
+ if (k>j) nrerror("backtrack failed in qm");
+
+ backtrack_qm1(k,j);
+
+ if (k<i+TURN) break; /* no more pairs */
+ r = urn() * (qm[ii-(k-1)] + expMLbase[k-i]);
+ if (expMLbase[k-i] >= r) break; /* no more pairs */
+ j = k-1;
+ }
+ }
+}
+
+PUBLIC void compute_probabilities(double FAB, double FA,double FB,
+ struct plist *prAB,
+ struct plist *prA, struct plist *prB,
+ int Alength) {
+ /*computes binding probabilities and dimer free energies*/
+ int i, j;
+ double pAB;
+ double mykT;
+ struct plist *lp1, *lp2;
+ int offset;
+
+ mykT=pf_params->kT/1000.;
+
+ /* pair probabilities in pr are relative to the null model (without DuplexInit) */
+
+ /*Compute probabilities pAB, pAA, pBB*/
+
+ pAB=1.-exp((1/mykT)*(FAB-FA-FB));
+
+ /* compute pair probabilities given that it is a dimer */
+ /* AB dimer */
+ offset=0;
+ lp2=prA;
+ if (pAB>0)
+ for (lp1=prAB; lp1->j>0; lp1++) {
+ float pp=0;
+ i=lp1->i; j=lp1->j;
+ while (offset+lp2->i < i && lp2->i>0) lp2++;
+ if (offset+lp2->i == i)
+ while ((offset+lp2->j) < j && (lp2->j>0)) lp2++;
+ if (lp2->j == 0) {lp2=prB; offset=Alength;}/* jump to next list */
+ if ((offset+lp2->i==i) && (offset+lp2->j ==j)) {
+ pp = lp2->p;
+ lp2++;
+ }
+ lp1->p=(lp1->p-(1-pAB)*pp)/pAB;
+ if(lp1->p < 0.){
+ warn_user("part_func_co: numeric instability detected, probability below zero!");
+ lp1->p = 0.;
+ }
+ }
+ return;
+}
+
+PRIVATE double *Newton_Conc(double KAB, double KAA, double KBB, double concA, double concB,double* ConcVec) {
+ double TOL, EPS, xn, yn, det, cA, cB;
+ int i=0;
+ /*Newton iteration for computing concentrations*/
+ cA=concA;
+ cB=concB;
+ TOL=1e-6; /*Tolerance for convergence*/
+ ConcVec=(double*)space(5*sizeof(double)); /* holds concentrations */
+ do {
+ /* det = (4.0 * KAA * cA + KAB *cB + 1.0) * (4.0 * KBB * cB + KAB *cA + 1.0) - (KAB *cB) * (KAB *cA); */
+ det = 1 + 16. *KAA*KBB*cA*cB + KAB*(cA+cB) + 4.*KAA*cA + 4.*KBB*cB + 4.*KAB*(KBB*cB*cB + KAA*cA*cA);
+ /* xn = ( (2.0 * KBB * cB*cB + KAB *cA *cB + cB - concB) * (KAB *cA) -
+ (2.0 * KAA * cA*cA + KAB *cA *cB + cA - concA) * (4.0 * KBB * cB + KAB *cA + 1.0) ) /det; */
+ xn = ( (2.0 * KBB * cB*cB + cB - concB) * (KAB *cA) - KAB*cA*cB*(4. * KBB*cB + 1.) -
+ (2.0 * KAA * cA*cA + cA - concA) * (4.0 * KBB * cB + KAB *cA + 1.0) ) /det;
+ /* yn = ( (2.0 * KAA * cA*cA + KAB *cA *cB + cA - concA) * (KAB *cB) -
+ (2.0 * KBB * cB*cB + KAB *cA *cB + cB - concB) * (4.0 * KAA * cA + KAB *cB + 1.0) ) /det; */
+ yn = ( (2.0 * KAA * cA*cA + cA - concA) * (KAB *cB) - KAB*cA*cB*(4. * KAA*cA + 1.) -
+ (2.0 * KBB * cB*cB + cB - concB) * (4.0 * KAA * cA + KAB *cB + 1.0) ) /det;
+ EPS = fabs(xn/cA) + fabs(yn/cB);
+ cA += xn;
+ cB += yn;
+ i++;
+ if (i>10000) {
+ fprintf(stderr, "Newton did not converge after %d steps!!\n",i);
+ break;
+ }
+ } while(EPS>TOL);
+
+ ConcVec[0]= cA*cB*KAB ;/*AB concentration*/
+ ConcVec[1]= cA*cA*KAA ;/*AA concentration*/
+ ConcVec[2]= cB*cB*KBB ;/*BB concentration*/
+ ConcVec[3]= cA; /* A concentration*/
+ ConcVec[4]= cB; /* B concentration*/
+
+ return ConcVec;
+}
+
+PUBLIC struct ConcEnt *get_concentrations(double FcAB, double FcAA, double FcBB, double FEA, double FEB, double *startconc)
+{
+ /*takes an array of start concentrations, computes equilibrium concentrations of dimers, monomers, returns array of concentrations in strucutre ConcEnt*/
+ double *ConcVec;
+ int i;
+ struct ConcEnt *Concentration;
+ double KAA, KAB, KBB, kT;
+
+ kT=pf_params->kT/1000.;
+ Concentration=(struct ConcEnt *)space(20*sizeof(struct ConcEnt));
+ /* Compute equilibrium constants */
+ /* again note the input free energies are not from the null model (without DuplexInit) */
+
+ KAA = exp(( 2.0 * FEA - FcAA)/kT);
+ KBB = exp(( 2.0 * FEB - FcBB)/kT);
+ KAB = exp(( FEA + FEB - FcAB)/kT);
+ /* printf("Kaa..%g %g %g\n", KAA, KBB, KAB); */
+ for (i=0; ((startconc[i]!=0)||(startconc[i+1]!=0));i+=2) {
+ ConcVec=Newton_Conc(KAB, KAA, KBB, startconc[i], startconc[i+1], ConcVec);
+ Concentration[i/2].A0=startconc[i];
+ Concentration[i/2].B0=startconc[i+1];
+ Concentration[i/2].ABc=ConcVec[0];
+ Concentration[i/2].AAc=ConcVec[1];
+ Concentration[i/2].BBc=ConcVec[2];
+ Concentration[i/2].Ac=ConcVec[3];
+ Concentration[i/2].Bc=ConcVec[4];
+
+ if (!(((i+2)/2)%20)) {
+ Concentration=(struct ConcEnt *)xrealloc(Concentration,((i+2)/2+20)*sizeof(struct ConcEnt));
+ }
+ free(ConcVec);
+ }
+
+ return Concentration;
+}
+
+PUBLIC FLT_OR_DBL *export_co_bppm(void){
+ return probs;
+}
+
+/*###########################################*/
+/*# deprecated functions below #*/
+/*###########################################*/
+
+
+PUBLIC struct plist *get_plist(struct plist *pl, int length, double cut_off) {
+ int i, j,n, count;
+ /*get pair probibilities out of pr array*/
+ count=0;
+ n=2;
+ for (i=1; i<length; i++) {
+ for (j=i+1; j<=length; j++) {
+ if (pr[my_iindx[i]-j]<cut_off) continue;
+ if (count==n*length-1) {
+ n*=2;
+ pl=(struct plist *)xrealloc(pl,n*length*sizeof(struct plist));
+ }
+ pl[count].i=i;
+ pl[count].j=j;
+ pl[count++].p=pr[my_iindx[i]-j];
+ /* printf("gpl: %2d %2d %.9f\n",i,j,pr[my_iindx[i]-j]);*/
+ }
+ }
+ pl[count].i=0;
+ pl[count].j=0; /*->??*/
+ pl[count++].p=0.;
+ pl=(struct plist *)xrealloc(pl,(count)*sizeof(struct plist));
+ return pl;
+}
+
+PUBLIC void init_co_pf_fold(int length){ /* DO NOTHING */ }
git://source.jalview.org / jabaws.git / blobdiff