Long-distance potentials: an approach to the multiple-minima problem in ligand-receptor interaction.
The multiple-minima problem is a classical problem in molecular structure prediction. For ligand-receptor systems, a possible direction to alleviate this major obstacle is to simplify the objective function (intermolecular energy) and smooth its profile. We introduce long-distance atom-atom potentials for ligand-receptor interactions. The longer ranges result in averaging of the energy potential at a given point. Our simplified force field is based on a trivial empirical representation of interatomic interactions as a step function. We demonstrate that the intermolecular energy calculation by a systematic search with such a simplified long-distance force field delivers the global minimum (crystallographically determined position of the ligand) by radically suppressing local minima (or false-positive fits). The effectiveness of the approach is demonstrated on different molecular complexes of known structure.
Vakser
I A
IA
Center for Molecular Design, Washington University, St Louis, MO 63130, USA.
D000465:Algorithms; D007611:Aprotinin / Q000737:chemistry; D018360:Crystallography, X-Ray; D006454:Hemoglobins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry
D006454:Hemoglobins; D008024:Ligands; D011506:Proteins; C100003:deoxyhemoglobin; D007611:Aprotinin; D014357:Trypsin