--- /dev/null
+#ifndef __VIENNA_RNA_PACKAGE_LOOP_ENERGIES_H__
+#define __VIENNA_RNA_PACKAGE_LOOP_ENERGIES_H__
+
+#include <stdio.h>
+#include <stdlib.h>
+#include <math.h>
+#include <ctype.h>
+#include <string.h>
+#include "params.h"
+#include "fold_vars.h"
+#include "energy_par.h"
+
+#ifdef __GNUC__
+# define INLINE inline
+#else
+# define INLINE
+#endif
+
+/**
+ * \file loop_energies.h
+ * \brief Energy evaluation for MFE and partition function calculations
+ *
+ * <P>
+ * This file contains functions for the calculation of the free energy \f$\Delta G\f$
+ * of a hairpin- [ E_Hairpin() ] or interior-loop [ E_IntLoop()] .<BR>
+ * The unit of the free energy returned is \f$10^{-2} * \mathrm{kcal}/\mathrm{mol}\f$
+ * </P>
+ * <P>
+ * In case of computing the partition function, this file also supplies functions
+ * which return the Boltzmann weights \f$e^{-\Delta G/kT} \f$ for a hairpin- [ exp_E_Hairpin() ]
+ * or interior-loop [ exp_E_IntLoop() ].
+ * </P>
+ */
+
+/**
+ * \def E_MLstem(A,B,C,D)
+ * <H2>Compute the Energy contribution of a Multiloop stem</H2>
+ * This definition is a wrapper for the E_Stem() funtion.
+ * It is substituted by an E_Stem() funtion call with argument
+ * extLoop=0, so the energy contribution returned reflects a
+ * stem introduced in a multiloop.<BR>
+ * As for the parameters B (si1) and C (sj1) of the substituted
+ * E_Stem() function, you can inhibit to take 5'-, 3'-dangles
+ * or mismatch contributions to be taken into account by passing
+ * -1 to these parameters.
+ *
+ * \see E_Stem()
+ * \param A The pair type of the stem-closing pair
+ * \param B The 5'-mismatching nucleotide
+ * \param C The 3'-mismatching nucleotide
+ * \param D The datastructure containing scaled energy parameters
+ * \return The energy contribution of the introduced multiloop stem
+ */
+INLINE PRIVATE int E_MLstem( int type,
+ int si1,
+ int sj1,
+ paramT *P);
+
+/**
+ * \def exp_E_MLstem(A,B,C,D)
+ * This is the partition function variant of \ref E_MLstem()
+ * \see E_MLstem()
+ * \return The Boltzmann weighted energy contribution of the introduced multiloop stem
+ */
+INLINE PRIVATE double exp_E_MLstem(int type,
+ int si1,
+ int sj1,
+ pf_paramT *P);
+
+/**
+ * \def E_ExtLoop(A,B,C,D)
+ * <H2>Compute the Energy contribution of an Exterior loop stem</H2>
+ * This definition is a wrapper for the E_Stem() funtion.
+ * It is substituted by an E_Stem() funtion call with argument
+ * extLoop=1, so the energy contribution returned reflects a
+ * stem introduced in an exterior-loop.<BR>
+ * As for the parameters B (si1) and C (sj1) of the substituted
+ * E_Stem() function, you can inhibit to take 5'-, 3'-dangles
+ * or mismatch contributions to be taken into account by passing
+ * -1 to these parameters.
+ *
+ * \see E_Stem()
+ * \param A The pair type of the stem-closing pair
+ * \param B The 5'-mismatching nucleotide
+ * \param C The 3'-mismatching nucleotide
+ * \param D The datastructure containing scaled energy parameters
+ * \return The energy contribution of the introduced exterior-loop stem
+ */
+INLINE PRIVATE int E_ExtLoop(int type,
+ int si1,
+ int sj1,
+ paramT *P);
+
+/**
+ * \def exp_E_ExtLoop(A,B,C,D)
+ * This is the partition function variant of \ref E_ExtLoop()
+ * \see E_ExtLoop()
+ * \return The Boltzmann weighted energy contribution of the introduced exterior-loop stem
+ */
+INLINE PRIVATE double exp_E_ExtLoop( int type,
+ int si1,
+ int sj1,
+ pf_paramT *P);
+
+/**
+ * <H2>Compute the Energy of an interior-loop</H2>
+ * This function computes the free energy \f$\Delta G\f$ of an interior-loop with the
+ * following structure: <BR>
+ * <PRE>
+ * 3' 5'
+ * | |
+ * U - V
+ * a_n b_1
+ * . .
+ * . .
+ * . .
+ * a_1 b_m
+ * X - Y
+ * | |
+ * 5' 3'
+ * </PRE>
+ * This general structure depicts an interior-loop that is closed by the base pair (X,Y).
+ * The enclosed base pair is (V,U) which leaves the unpaired bases a_1-a_n and b_1-b_n
+ * that constitute the loop. In this example, the length of the interior-loop is \f$(n+m)\f$
+ * where n or m may be 0 resulting in a bulge-loop or base pair stack.
+ * The mismatching nucleotides for the closing pair (X,Y) are:<BR>
+ * 5'-mismatch: a_1<BR>
+ * 3'-mismatch: b_m<BR>
+ * and for the enclosed base pair (V,U):<BR>
+ * 5'-mismatch: b_1<BR>
+ * 3'-mismatch: a_n<BR>
+ * \note Base pairs are always denoted in 5'->3' direction. Thus the enclosed base pair
+ * must be 'turned arround' when evaluating the free energy of the interior-loop
+ * \see scale_parameters()
+ * \see paramT
+ * \note This function is threadsafe
+ *
+ * \param n1 The size of the 'left'-loop (number of unpaired nucleotides)
+ * \param n2 The size of the 'right'-loop (number of unpaired nucleotides)
+ * \param type The pair type of the base pair closing the interior loop
+ * \param type_2 The pair type of the enclosed base pair
+ * \param si1 The 5'-mismatching nucleotide of the closing pair
+ * \param sj1 The 3'-mismatching nucleotide of the closing pair
+ * \param sp1 The 3'-mismatching nucleotide of the enclosed pair
+ * \param sq1 The 5'-mismatching nucleotide of the enclosed pair
+ * \param P The datastructure containing scaled energy parameters
+ * \return The Free energy of the Interior-loop in dcal/mol
+ */
+INLINE PRIVATE int E_IntLoop(int n1,
+ int n2,
+ int type,
+ int type_2,
+ int si1,
+ int sj1,
+ int sp1,
+ int sq1,
+ paramT *P);
+
+
+/**
+ * <H2>Compute the Energy of a hairpin-loop</H2>
+ * To evaluate the free energy of a hairpin-loop, several parameters have to be known.
+ * A general hairpin-loop has this structure:<BR>
+ * <PRE>
+ * a3 a4
+ * a2 a5
+ * a1 a6
+ * X - Y
+ * | |
+ * 5' 3'
+ * </PRE>
+ * where X-Y marks the closing pair [e.g. a <B>(G,C)</B> pair]. The length of this loop is 6 as there are
+ * six unpaired nucleotides (a1-a6) enclosed by (X,Y). The 5' mismatching nucleotide is
+ * a1 while the 3' mismatch is a6. The nucleotide sequence of this loop is "a1.a2.a3.a4.a5.a6" <BR>
+ * \note The parameter sequence should contain the sequence of the loop in capital letters of the nucleic acid
+ * alphabet if the loop size is below 7. This is useful for unusually stable tri-, tetra- and hexa-loops
+ * which are treated differently (based on experimental data) if they are tabulated.
+ * @see scale_parameters()
+ * @see paramT
+ * \warning Not (really) thread safe! A threadsafe implementation will replace this function in a future release!\n
+ * Energy evaluation may change due to updates in global variable "tetra_loop"
+ *
+ * \param size The size of the loop (number of unpaired nucleotides)
+ * \param type The pair type of the base pair closing the hairpin
+ * \param si1 The 5'-mismatching nucleotide
+ * \param sj1 The 3'-mismatching nucleotide
+ * \param string The sequence of the loop
+ * \param P The datastructure containing scaled energy parameters
+ * \return The Free energy of the Hairpin-loop in dcal/mol
+ */
+INLINE PRIVATE int E_Hairpin(int size,
+ int type,
+ int si1,
+ int sj1,
+ const char *string,
+ paramT *P);
+
+/**
+ * <H2>Compute the energy contribution of a stem branching off a loop-region</H2>
+ * This function computes the energy contribution of a stem that branches off
+ * a loop region. This can be the case in multiloops, when a stem branching off
+ * increases the degree of the loop but also <I>immediately interior base pairs</I>
+ * of an exterior loop contribute free energy.
+ * To switch the bahavior of the function according to the evaluation of a multiloop-
+ * or exterior-loop-stem, you pass the flag 'extLoop'.
+ * The returned energy contribution consists of a TerminalAU penalty if the pair type
+ * is greater than 2, dangling end contributions of mismatching nucleotides adjacent to
+ * the stem if only one of the si1, sj1 parameters is greater than 0 and mismatch energies
+ * if both mismatching nucleotides are positive values.
+ * Thus, to avoid incooperating dangling end or mismatch energies just pass a negative number,
+ * e.g. -1 to the mismatch argument.
+ *
+ * This is an illustration of how the energy contribution is assembled:
+ * <PRE>
+ * 3' 5'
+ * | |
+ * X - Y
+ * 5'-si1 sj1-3'
+ * </PRE>
+ *
+ * Here, (X,Y) is the base pair that closes the stem that branches off a loop region.
+ * The nucleotides si1 and sj1 are the 5'- and 3'- mismatches, respectively. If the base pair
+ * type of (X,Y) is greater than 2 (i.e. an A-U or G-U pair, the TerminalAU penalty will be
+ * included in the energy contribution returned. If si1 and sj1 are both nonnegative numbers,
+ * mismatch energies will also be included. If one of sij or sj1 is a negtive value, only
+ * 5' or 3' dangling end contributions are taken into account. To prohibit any of these mismatch
+ * contributions to be incoorporated, just pass a negative number to both, si1 and sj1.
+ * In case the argument extLoop is 0, the returned energy contribution also includes
+ * the <I>internal-loop-penalty</I> of a multiloop stem with closing pair type.
+ *
+ * \see E_MLstem()
+ * \see E_ExtLoop()
+ * \note This function is threadsafe
+ *
+ * \param type The pair type of the first base pair un the stem
+ * \param si1 The 5'-mismatching nucleotide
+ * \param sj1 The 3'-mismatching nucleotide
+ * \param extLoop A flag that indicates whether the contribution reflects the one of an exterior loop or not
+ * \param P The datastructure containing scaled energy parameters
+ * \return The Free energy of the branch off the loop in dcal/mol
+ *
+ */
+INLINE PRIVATE int E_Stem( int type,
+ int si1,
+ int sj1,
+ int extLoop,
+ paramT *P);
+
+/**
+ * <H2>Compute the Boltzmann weighted energy contribution of a stem branching off a loop-region</H2>
+ * This is the partition function variant of \ref E_Stem()
+ * \see E_Stem()
+ * \note This function is threadsafe
+ *
+ * \return The Boltzmann weighted energy contribution of the branch off the loop
+ */
+INLINE PRIVATE double exp_E_Stem(int type,
+ int si1,
+ int sj1,
+ int extLoop,
+ pf_paramT *P);
+
+/**
+ * <H2>Compute Boltzmann weight \f$e^{-\Delta G/kT} \f$ of a hairpin loop</H2>
+ * multiply by scale[u+2]
+ * @see get_scaled_pf_parameters()
+ * @see pf_paramT
+ * @see E_Hairpin()
+ * \warning Not (really) thread safe! A threadsafe implementation will replace this function in a future release!\n
+ * Energy evaluation may change due to updates in global variable "tetra_loop"
+ *
+ * \param u The size of the loop (number of unpaired nucleotides)
+ * \param type The pair type of the base pair closing the hairpin
+ * \param si1 The 5'-mismatching nucleotide
+ * \param sj1 The 3'-mismatching nucleotide
+ * \param string The sequence of the loop
+ * \param P The datastructure containing scaled Boltzmann weights of the energy parameters
+ * \return The Boltzmann weight of the Hairpin-loop
+ */
+INLINE PRIVATE double exp_E_Hairpin( int u,
+ int type,
+ short si1,
+ short sj1,
+ const char *string,
+ pf_paramT *P);
+
+/**
+ * <H2>Compute Boltzmann weight \f$e^{-\Delta G/kT} \f$ of interior loop</H2>
+ * multiply by scale[u1+u2+2] for scaling
+ * @see get_scaled_pf_parameters()
+ * @see pf_paramT
+ * @see E_IntLoop()
+ * \note This function is threadsafe
+ *
+ * \param u1 The size of the 'left'-loop (number of unpaired nucleotides)
+ * \param u2 The size of the 'right'-loop (number of unpaired nucleotides)
+ * \param type The pair type of the base pair closing the interior loop
+ * \param type2 The pair type of the enclosed base pair
+ * \param si1 The 5'-mismatching nucleotide of the closing pair
+ * \param sj1 The 3'-mismatching nucleotide of the closing pair
+ * \param sp1 The 3'-mismatching nucleotide of the enclosed pair
+ * \param sq1 The 5'-mismatching nucleotide of the enclosed pair
+ * \param P The datastructure containing scaled Boltzmann weights of the energy parameters
+ * \return The Boltzmann weight of the Interior-loop
+ */
+INLINE PRIVATE double exp_E_IntLoop(int u1,
+ int u2,
+ int type,
+ int type2,
+ short si1,
+ short sj1,
+ short sp1,
+ short sq1,
+ pf_paramT *P);
+
+
+/*
+#################################
+# BEGIN OF FUNCTION DEFINITIONS #
+#################################
+*/
+INLINE PRIVATE int E_Hairpin(int size, int type, int si1, int sj1, const char *string, paramT *P){
+ int energy;
+
+ energy = (size <= 30) ? P->hairpin[size] : P->hairpin[30]+(int)(P->lxc*log((size)/30.));
+ if (P->model_details.special_hp){
+ if (size == 4) { /* check for tetraloop bonus */
+ char tl[7]={0}, *ts;
+ strncpy(tl, string, 6);
+ if ((ts=strstr(P->Tetraloops, tl)))
+ return (P->Tetraloop_E[(ts - P->Tetraloops)/7]);
+ }
+ else if (size == 6) {
+ char tl[9]={0}, *ts;
+ strncpy(tl, string, 8);
+ if ((ts=strstr(P->Hexaloops, tl)))
+ return (energy = P->Hexaloop_E[(ts - P->Hexaloops)/9]);
+ }
+ else if (size == 3) {
+ char tl[6]={0,0,0,0,0,0}, *ts;
+ strncpy(tl, string, 5);
+ if ((ts=strstr(P->Triloops, tl))) {
+ return (P->Triloop_E[(ts - P->Triloops)/6]);
+ }
+ return (energy + (type>2 ? P->TerminalAU : 0));
+ }
+ }
+ energy += P->mismatchH[type][si1][sj1];
+
+ return energy;
+}
+
+INLINE PRIVATE int E_IntLoop(int n1, int n2, int type, int type_2, int si1, int sj1, int sp1, int sq1, paramT *P){
+ /* compute energy of degree 2 loop (stack bulge or interior) */
+ int nl, ns, energy;
+ energy = INF;
+
+ if (n1>n2) { nl=n1; ns=n2;}
+ else {nl=n2; ns=n1;}
+
+ if (nl == 0)
+ return P->stack[type][type_2]; /* stack */
+
+ if (ns==0) { /* bulge */
+ energy = (nl<=MAXLOOP)?P->bulge[nl]:
+ (P->bulge[30]+(int)(P->lxc*log(nl/30.)));
+ if (nl==1) energy += P->stack[type][type_2];
+ else {
+ if (type>2) energy += P->TerminalAU;
+ if (type_2>2) energy += P->TerminalAU;
+ }
+ return energy;
+ }
+ else { /* interior loop */
+ if (ns==1) {
+ if (nl==1) /* 1x1 loop */
+ return P->int11[type][type_2][si1][sj1];
+ if (nl==2) { /* 2x1 loop */
+ if (n1==1)
+ energy = P->int21[type][type_2][si1][sq1][sj1];
+ else
+ energy = P->int21[type_2][type][sq1][si1][sp1];
+ return energy;
+ }
+ else { /* 1xn loop */
+ energy = (nl+1<=MAXLOOP)?(P->internal_loop[nl+1]) : (P->internal_loop[30]+(int)(P->lxc*log((nl+1)/30.)));
+ energy += MIN2(MAX_NINIO, (nl-ns)*P->ninio[2]);
+ energy += P->mismatch1nI[type][si1][sj1] + P->mismatch1nI[type_2][sq1][sp1];
+ return energy;
+ }
+ }
+ else if (ns==2) {
+ if(nl==2) { /* 2x2 loop */
+ return P->int22[type][type_2][si1][sp1][sq1][sj1];}
+ else if (nl==3){ /* 2x3 loop */
+ energy = P->internal_loop[5]+P->ninio[2];
+ energy += P->mismatch23I[type][si1][sj1] + P->mismatch23I[type_2][sq1][sp1];
+ return energy;
+ }
+
+ }
+ { /* generic interior loop (no else here!)*/
+ energy = (n1+n2<=MAXLOOP)?(P->internal_loop[n1+n2]) : (P->internal_loop[30]+(int)(P->lxc*log((n1+n2)/30.)));
+
+ energy += MIN2(MAX_NINIO, (nl-ns)*P->ninio[2]);
+
+ energy += P->mismatchI[type][si1][sj1] + P->mismatchI[type_2][sq1][sp1];
+ }
+ }
+ return energy;
+}
+
+INLINE PRIVATE int E_Stem(int type, int si1, int sj1, int extLoop, paramT *P){
+ int energy = 0;
+ int d5 = (si1 >= 0) ? P->dangle5[type][si1] : 0;
+ int d3 = (sj1 >= 0) ? P->dangle3[type][sj1] : 0;
+
+ if(type > 2)
+ energy += P->TerminalAU;
+
+ if(si1 >= 0 && sj1 >= 0)
+ energy += (extLoop) ? P->mismatchExt[type][si1][sj1] : P->mismatchM[type][si1][sj1];
+ else
+ energy += d5 + d3;
+
+ if(!extLoop) energy += P->MLintern[type];
+ return energy;
+}
+
+INLINE PRIVATE int E_ExtLoop(int type, int si1, int sj1, paramT *P){
+ int energy = 0;
+ if(si1 >= 0 && sj1 >= 0){
+ energy += P->mismatchExt[type][si1][sj1];
+ }
+ else if (si1 >= 0){
+ energy += P->dangle5[type][si1];
+ }
+ else if (sj1 >= 0){
+ energy += P->dangle3[type][sj1];
+ }
+
+ if(type > 2)
+ energy += P->TerminalAU;
+
+ return energy;
+}
+
+INLINE PRIVATE int E_MLstem(int type, int si1, int sj1, paramT *P){
+ int energy = 0;
+ if(si1 >= 0 && sj1 >= 0){
+ energy += P->mismatchM[type][si1][sj1];
+ }
+ else if (si1 >= 0){
+ energy += P->dangle5[type][si1];
+ }
+ else if (sj1 >= 0){
+ energy += P->dangle3[type][sj1];
+ }
+
+ if(type > 2)
+ energy += P->TerminalAU;
+
+ energy += P->MLintern[type];
+
+ return energy;
+}
+
+INLINE PRIVATE double exp_E_Hairpin(int u, int type, short si1, short sj1, const char *string, pf_paramT *P){
+ double q, kT;
+ kT = P->kT; /* kT in cal/mol */
+
+ if(u <= 30)
+ q = P->exphairpin[u];
+ else
+ q = P->exphairpin[30] * exp( -(P->lxc*log( u/30.))*10./kT);
+
+ if(u < 3) return q; /* should only be the case when folding alignments */
+
+ if ((P->model_details.special_hp)&&(u==4)) {
+ char tl[7]={0,0,0,0,0,0,0}, *ts;
+ strncpy(tl, string, 6);
+ if ((ts=strstr(P->Tetraloops, tl))){
+ if(type != 7)
+ return (P->exptetra[(ts-P->Tetraloops)/7]);
+ else
+ q *= P->exptetra[(ts-P->Tetraloops)/7];
+ }
+ }
+ if ((tetra_loop)&&(u==6)) {
+ char tl[9]={0,0,0,0,0,0,0,0,0}, *ts;
+ strncpy(tl, string, 6);
+ if ((ts=strstr(P->Hexaloops, tl)))
+ return (P->exphex[(ts-P->Hexaloops)/9]);
+ }
+ if (u==3) {
+ char tl[6]={0,0,0,0,0,0}, *ts;
+ strncpy(tl, string, 5);
+ if ((ts=strstr(P->Triloops, tl)))
+ return (P->exptri[(ts-P->Triloops)/6]);
+ if (type>2)
+ q *= P->expTermAU;
+ }
+ else /* no mismatches for tri-loops */
+ q *= P->expmismatchH[type][si1][sj1];
+
+ return q;
+}
+
+INLINE PRIVATE double exp_E_IntLoop(int u1, int u2, int type, int type2, short si1, short sj1, short sp1, short sq1, pf_paramT *P){
+ int ul, us, no_close = 0;
+ double z = 0.;
+
+ if ((no_closingGU) && ((type2==3)||(type2==4)||(type==3)||(type==4)))
+ no_close = 1;
+
+ if (u1>u2) { ul=u1; us=u2;}
+ else {ul=u2; us=u1;}
+
+ if (ul==0) /* stack */
+ z = P->expstack[type][type2];
+ else if(!no_close){
+ if (us==0) { /* bulge */
+ z = P->expbulge[ul];
+ if (ul==1) z *= P->expstack[type][type2];
+ else {
+ if (type>2) z *= P->expTermAU;
+ if (type2>2) z *= P->expTermAU;
+ }
+ return z;
+ }
+ else if (us==1) {
+ if (ul==1){ /* 1x1 loop */
+ return P->expint11[type][type2][si1][sj1];
+ }
+ if (ul==2) { /* 2x1 loop */
+ if (u1==1)
+ return P->expint21[type][type2][si1][sq1][sj1];
+ else
+ return P->expint21[type2][type][sq1][si1][sp1];
+ }
+ else { /* 1xn loop */
+ z = P->expinternal[ul+us] * P->expmismatch1nI[type][si1][sj1] * P->expmismatch1nI[type2][sq1][sp1];
+ return z * P->expninio[2][ul-us];
+ }
+ }
+ else if (us==2) {
+ if(ul==2) /* 2x2 loop */
+ return P->expint22[type][type2][si1][sp1][sq1][sj1];
+ else if(ul==3){ /* 2x3 loop */
+ z = P->expinternal[5]*P->expmismatch23I[type][si1][sj1]*P->expmismatch23I[type2][sq1][sp1];
+ return z * P->expninio[2][1];
+ }
+ }
+ /* generic interior loop (no else here!)*/
+ z = P->expinternal[ul+us] * P->expmismatchI[type][si1][sj1] * P->expmismatchI[type2][sq1][sp1];
+ return z * P->expninio[2][ul-us];
+
+ }
+ return z;
+}
+
+INLINE PRIVATE double exp_E_Stem(int type, int si1, int sj1, int extLoop, pf_paramT *P){
+ double energy = 1.0;
+ double d5 = (si1 >= 0) ? P->expdangle5[type][si1] : 1.;
+ double d3 = (sj1 >= 0) ? P->expdangle3[type][sj1] : 1.;
+
+ if(type > 2)
+ energy *= P->expTermAU;
+
+ if(si1 >= 0 && sj1 >= 0)
+ energy *= (extLoop) ? P->expmismatchExt[type][si1][sj1] : P->expmismatchM[type][si1][sj1];
+ else
+ energy *= d5 * d3;
+
+ if(!extLoop) energy *= P->expMLintern[type];
+ return energy;
+}
+
+INLINE PRIVATE double exp_E_MLstem(int type, int si1, int sj1, pf_paramT *P){
+ double energy = 1.0;
+ if(si1 >= 0 && sj1 >= 0){
+ energy *= P->expmismatchM[type][si1][sj1];
+ }
+ else if(si1 >= 0){
+ energy *= P->expdangle5[type][si1];
+ }
+ else if(sj1 >= 0){
+ energy *= P->expdangle3[type][sj1];
+ }
+
+ if(type > 2)
+ energy *= P->expTermAU;
+
+ energy *= P->expMLintern[type];
+ return energy;
+}
+
+INLINE PRIVATE double exp_E_ExtLoop(int type, int si1, int sj1, pf_paramT *P){
+ double energy = 1.0;
+ if(si1 >= 0 && sj1 >= 0){
+ energy *= P->expmismatchExt[type][si1][sj1];
+ }
+ else if(si1 >= 0){
+ energy *= P->expdangle5[type][si1];
+ }
+ else if(sj1 >= 0){
+ energy *= P->expdangle3[type][sj1];
+ }
+
+ if(type > 2)
+ energy *= P->expTermAU;
+
+ return energy;
+}
+
+INLINE PRIVATE int E_IntLoop_Co(int type, int type_2, int i, int j, int p, int q, int cutpoint, short si1, short sj1, short sp1, short sq1, int dangles, paramT *P){
+ int energy = 0;
+ if(type > 2) energy += P->TerminalAU;
+ if(type_2 > 2) energy += P->TerminalAU;
+
+ if(!dangles) return energy;
+
+ int ci = (i>=cutpoint)||((i+1)<cutpoint);
+ int cj = ((j-1)>=cutpoint)||(j<cutpoint);
+ int cp = ((p-1)>=cutpoint)||(p<cutpoint);
+ int cq = (q>=cutpoint)||((q+1)<cutpoint);
+
+ int d3 = ci ? P->dangle3[type][si1] : 0;
+ int d5 = cj ? P->dangle5[type][sj1] : 0;
+ int d5_2 = cp ? P->dangle5[type_2][sp1] : 0;
+ int d3_2 = cq ? P->dangle3[type_2][sq1] : 0;
+
+ int tmm = (cj && ci) ? P->mismatchExt[type][sj1][si1] : d5 + d3;
+ int tmm_2 = (cp && cq) ? P->mismatchExt[type_2][sp1][sq1] : d5_2 + d3_2;
+
+ if(dangles == 2) return energy + tmm + tmm_2;
+
+ /* now we may have non-double dangles only */
+ if(i+2 < p){
+ if(q+2 < j){ energy += tmm + tmm_2;}
+ else if(q+2 == j){ energy += (cj && cq) ? MIN2(tmm + d5_2, tmm_2 + d3) : tmm + tmm_2;}
+ else energy += d3 + d5_2;
+ }
+ else if(i+2 == p){
+ if(q+2 < j){ energy += (ci && cp) ? MIN2(tmm + d3_2, tmm_2 + d5) : tmm + tmm_2;}
+ else if(q+2 == j){
+ energy += MIN2(tmm, MIN2(tmm_2, MIN2(d5 + d5_2, d3 + d3_2)));
+ }
+ else energy += MIN2(d3, d5_2);
+ }
+ else{
+ if(q+2 < j){ energy += d5 + d3_2;}
+ else if(q+2 == j){ energy += MIN2(d5, d3_2);}
+ }
+ return energy;
+}
+
+#endif