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38 /* This file is completely threadsafe - keep it that way! */
39 #include "gmxpre.h"
40 
41 #include "hizzie.h"
42 
43 #include <cmath>
44 #include <cstdio>
45 #include <cstring>
46 
47 #include "gromacs/fileio/pdbio.h"
48 #include "gromacs/gmxpreprocess/pdb2top.h"
49 #include "gromacs/gmxpreprocess/toputil.h"
50 #include "gromacs/math/functions.h"
51 #include "gromacs/math/units.h"
52 #include "gromacs/math/vec.h"
53 #include "gromacs/topology/block.h"
54 #include "gromacs/topology/symtab.h"
55 #include "gromacs/utility/arraysize.h"
56 #include "gromacs/utility/cstringutil.h"
57 #include "gromacs/utility/fatalerror.h"
58 #include "gromacs/utility/smalloc.h"
59 
in_strings(char * key,int nstr,const char ** str)60 static int in_strings(char* key, int nstr, const char** str)
61 {
62     int j;
63 
64     for (j = 0; (j < nstr); j++)
65     {
66         if (strcmp(str[j], key) == 0)
67         {
68             return j;
69         }
70     }
71 
72     return -1;
73 }
74 
hbond(rvec x[],int i,int j,real distance)75 static bool hbond(rvec x[], int i, int j, real distance)
76 {
77     real tol = distance * distance;
78     rvec tmp;
79 
80     rvec_sub(x[i], x[j], tmp);
81 
82     return (iprod(tmp, tmp) < tol);
83 }
84 
chk_allhb(t_atoms * pdba,rvec x[],t_blocka * hb,const bool donor[],const bool accept[],real dist)85 static void chk_allhb(t_atoms* pdba, rvec x[], t_blocka* hb, const bool donor[], const bool accept[], real dist)
86 {
87     int i, j, k, ii, natom;
88 
89     natom = pdba->nr;
90     snew(hb->index, natom + 1);
91     snew(hb->a, 6 * natom);
92     hb->nr  = natom;
93     hb->nra = 6 * natom;
94 
95     k = ii          = 0;
96     hb->index[ii++] = 0;
97     for (i = 0; (i < natom); i++)
98     {
99         if (donor[i])
100         {
101             for (j = i + 1; (j < natom); j++)
102             {
103                 if ((accept[j]) && (hbond(x, i, j, dist)))
104                 {
105                     hb->a[k++] = j;
106                 }
107             }
108         }
109         else if (accept[i])
110         {
111             for (j = i + 1; (j < natom); j++)
112             {
113                 if ((donor[j]) && (hbond(x, i, j, dist)))
114                 {
115                     hb->a[k++] = j;
116                 }
117             }
118         }
119         hb->index[ii++] = k;
120     }
121     hb->nra = k;
122 }
123 
chk_hbonds(int i,t_atoms * pdba,rvec x[],const bool ad[],bool hbond[],rvec xh,real angle,real dist)124 static bool chk_hbonds(int i, t_atoms* pdba, rvec x[], const bool ad[], bool hbond[], rvec xh, real angle, real dist)
125 {
126     bool bHB;
127     int  j, aj, ri, natom;
128     real d2, dist2, a;
129     rvec nh, oh;
130 
131     natom = pdba->nr;
132     bHB   = FALSE;
133     ri    = pdba->atom[i].resind;
134     dist2 = gmx::square(dist);
135     for (j = 0; (j < natom); j++)
136     {
137         /* Check whether the other atom is a donor/acceptor and not i */
138         if ((ad[j]) && (j != i))
139         {
140             /* Check whether the other atom is on the same ring as well */
141             if ((pdba->atom[j].resind != ri)
142                 || ((strcmp(*pdba->atomname[j], "ND1") != 0) && (strcmp(*pdba->atomname[j], "NE2") != 0)))
143             {
144                 aj = j;
145                 d2 = distance2(x[i], x[j]);
146                 rvec_sub(x[i], xh, nh);
147                 rvec_sub(x[aj], xh, oh);
148                 a = RAD2DEG * acos(cos_angle(nh, oh));
149                 if ((d2 < dist2) && (a > angle))
150                 {
151                     hbond[i] = TRUE;
152                     bHB      = TRUE;
153                 }
154             }
155         }
156     }
157     return bHB;
158 }
159 
calc_ringh(rvec xattach,rvec xb,rvec xc,rvec xh)160 static void calc_ringh(rvec xattach, rvec xb, rvec xc, rvec xh)
161 {
162     rvec tab, tac;
163     real n;
164 
165     /* Add a proton on a ring to atom attach at distance 0.1 nm */
166     rvec_sub(xattach, xb, tab);
167     rvec_sub(xattach, xc, tac);
168     rvec_add(tab, tac, xh);
169     n = 0.1 / norm(xh);
170     svmul(n, xh, xh);
171     rvec_inc(xh, xattach);
172 }
173 
set_histp(t_atoms * pdba,rvec * x,t_symtab * symtab,real angle,real dist)174 void set_histp(t_atoms* pdba, rvec* x, t_symtab* symtab, real angle, real dist)
175 {
176     static const char* prot_acc[] = { "O", "OD1", "OD2", "OE1", "OE2", "OG", "OG1", "OH", "OW" };
177 #define NPA asize(prot_acc)
178     static const char* prot_don[] = { "N",  "NH1", "NH2", "NE", "ND1", "ND2", "NE2",
179                                       "NZ", "OG",  "OG1", "OH", "NE1", "OW" };
180 #define NPD asize(prot_don)
181 
182     bool *    donor, *acceptor;
183     bool*     hbond;
184     bool      bHDd, bHEd;
185     rvec      xh1, xh2;
186     int       natom;
187     int       i, j, nd, na, hisind, type = -1;
188     int       nd1, ne2, cg, cd2, ce1;
189     t_blocka* hb;
190     char*     atomnm;
191 
192     natom = pdba->nr;
193 
194     i = 0;
195     while (i < natom && gmx_strcasecmp(*pdba->resinfo[pdba->atom[i].resind].name, "HIS") != 0)
196     {
197         i++;
198     }
199     if (natom == i)
200     {
201         return;
202     }
203 
204     /* A histidine residue exists that requires automated assignment, so
205      * doing the analysis of donors and acceptors is worthwhile. */
206     fprintf(stderr,
207             "Analysing hydrogen-bonding network for automated assignment of histidine\n"
208             " protonation.");
209 
210     snew(donor, natom);
211     snew(acceptor, natom);
212     snew(hbond, natom);
213     snew(hb, 1);
214 
215     nd = na = 0;
216     for (j = 0; (j < natom); j++)
217     {
218         if (in_strings(*pdba->atomname[j], NPA, prot_acc) != -1)
219         {
220             acceptor[j] = TRUE;
221             na++;
222         }
223         if (in_strings(*pdba->atomname[j], NPD, prot_don) != -1)
224         {
225             donor[j] = TRUE;
226             nd++;
227         }
228     }
229     fprintf(stderr, " %d donors and %d acceptors were found.\n", nd, na);
230     chk_allhb(pdba, x, hb, donor, acceptor, dist);
231     fprintf(stderr, "There are %d hydrogen bonds\n", hb->nra);
232 
233     /* Now do the HIS stuff */
234     hisind = -1;
235     while (i < natom)
236     {
237         if (gmx_strcasecmp(*pdba->resinfo[pdba->atom[i].resind].name, "HIS") != 0)
238         {
239             i++;
240         }
241         else
242         {
243             if (pdba->atom[i].resind != hisind)
244             {
245                 hisind = pdba->atom[i].resind;
246 
247                 /* Find the  atoms in the ring */
248                 nd1 = ne2 = cg = cd2 = ce1 = -1;
249                 while (i < natom && pdba->atom[i].resind == hisind)
250                 {
251                     atomnm = *pdba->atomname[i];
252                     if (strcmp(atomnm, "CD2") == 0)
253                     {
254                         cd2 = i;
255                     }
256                     else if (strcmp(atomnm, "CG") == 0)
257                     {
258                         cg = i;
259                     }
260                     else if (strcmp(atomnm, "CE1") == 0)
261                     {
262                         ce1 = i;
263                     }
264                     else if (strcmp(atomnm, "ND1") == 0)
265                     {
266                         nd1 = i;
267                     }
268                     else if (strcmp(atomnm, "NE2") == 0)
269                     {
270                         ne2 = i;
271                     }
272 
273                     i++;
274                 }
275 
276                 if (!((cg == -1) || (cd2 == -1) || (ce1 == -1) || (nd1 == -1) || (ne2 == -1)))
277                 {
278                     calc_ringh(x[nd1], x[cg], x[ce1], xh1);
279                     calc_ringh(x[ne2], x[ce1], x[cd2], xh2);
280 
281                     bHDd = chk_hbonds(nd1, pdba, x, acceptor, hbond, xh1, angle, dist);
282                     chk_hbonds(nd1, pdba, x, donor, hbond, xh1, angle, dist);
283                     bHEd = chk_hbonds(ne2, pdba, x, acceptor, hbond, xh2, angle, dist);
284                     chk_hbonds(ne2, pdba, x, donor, hbond, xh2, angle, dist);
285 
286                     if (bHDd)
287                     {
288                         if (bHEd)
289                         {
290                             type = ehisH;
291                         }
292                         else
293                         {
294                             type = ehisA;
295                         }
296                     }
297                     else
298                     {
299                         type = ehisB;
300                     }
301                     fprintf(stderr, "Will use %s for residue %d\n", hh[type], pdba->resinfo[hisind].nr);
302                 }
303                 else
304                 {
305                     gmx_fatal(FARGS, "Incomplete ring in HIS%d", pdba->resinfo[hisind].nr);
306                 }
307 
308                 pdba->resinfo[hisind].rtp = put_symtab(symtab, hh[type]);
309             }
310         }
311     }
312     done_blocka(hb);
313     sfree(hb);
314     sfree(donor);
315     sfree(acceptor);
316     sfree(hbond);
317 }
318