Docking of conforrnationally flexible proteins

Bilha Sandak, Ruth Nussinov, Haim J. Wolfson*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

8 Scopus citations

Abstract

In this work we present and apply a 3-D pattern matching algorithm developed to solve structural recognition problems in molecular biology. The ability to automatically predict molecular interactions, is important in rational drug design and discovery, as well as a research tool in biomolecular structural recognition. Docking of a pair of molecules involves finding a proper partial fit between their molecular surfaces, as molecules interact at their surface. The generation of docked binding modes between two associating molecules depends on their 3-D structures and on their conformational flexibility, namely hinge-bending induced transitions. In hinge-bending, relatively rigid molecular subparts rotate on hinge(s) with respect to each other. This type of movements can occur in either of the two participating molecules, i.e., in the ligand or in the receptor molecule. Current automated docking techniques enable hinge bending flexibility in small ligands (e.g., drug molecules). Our approach allows hinge induced motions to exist in either diverse size ligands or variable size receptors (e.g., enzymes). We achieve this by the extension of the generalized Hough transform and Geometric Hashing techniques, which were originally developed for partially occluded articulated (flexible) object recognition in Computer Vision & Robotics. We show experimental results obtained by applying the algorithm on pairs of molecules allowing hinge-bending in either of the molecules for both complexed (bound) and unbound molecular configurations. We also discuss additional implications and applications of our approach.

Original languageEnglish
Title of host publicationCombinatorial Pattern Matching - 7th Annual Symposium, CPM 1996, Proceedings
EditorsGene Myers, Dan Hirschberg
PublisherSpringer Verlag
Pages271-287
Number of pages17
ISBN (Print)3540612580, 9783540612582
DOIs
StatePublished - 1996
Event7th Annual Symposium on Combinatorial Pattern Matching, CPM 1996 - Laguna Beach, United States
Duration: 10 Jun 199612 Jun 1996

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume1075
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference7th Annual Symposium on Combinatorial Pattern Matching, CPM 1996
Country/TerritoryUnited States
CityLaguna Beach
Period10/06/9612/06/96

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