A Point-Matching Based Algorithm for 3D Surface Alignment of Drug-Sized Molecules

Molecular shapes play an important role in molecular interactions, e.g., between a protein and a ligand. The ‘outer’ shape of a molecule can be approximated by its solvent excluded surface (SES). In this article we present a new approach to molecular surface alignment which is capable of identifying partial similarities. The approach utilizes an iterative point matching scheme which is applied to the points representing the SES. Our algorithm belongs to the multi-start methods. We first generate a number of initial alignments that are locally optimized by an iterative surface point matching algorithm which tries to maximize the number of matched points while minimizing the distance between the matched points. The algorithm identifies similar surface regions given by the matched surface points. This makes it well suited for multiple alignment of molecular surfaces. The subalgorithm proposed for distributing points uniformly across a surface might be of general interest for the comparison of molecular surfaces.

[1]  Ingrid Fischer,et al.  Computational life sciences II , 2005 .

[2]  B. Masek,et al.  Molecular surface comparisons , 1995 .

[3]  Christian Lemmen,et al.  Computational methods for the structural alignment of molecules , 2000, J. Comput. Aided Mol. Des..

[4]  David W. Ritchie,et al.  Fast computation, rotation, and comparison of low resolution spherical harmonic molecular surfaces , 1999, Journal of Computational Chemistry.

[5]  Tatsuya Akutsu.  Protein Structure Alignment Using a Graph Matching Technique , 1995 .

[6]  Oliver Deussen,et al.  Floating Points: A Method for Computing Stipple Drawings , 2000, Comput. Graph. Forum.

[7]  Daniel Baum.  Multiple Semi-flexible 3D Superposition of Drug-Sized Molecules , 2005, CompLife.

[8]  Craig Gotsman,et al.  Explicit Surface Remeshing , 2003, Symposium on Geometry Processing.

[9]  N. Stiefl,et al.  Mapping property distributions of molecular surfaces: algorithm and evaluation of a novel 3D quantitative structure-activity relationship technique. , 2003, Journal of medicinal chemistry.

[10]  T. Halgren.  Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 , 1996, J. Comput. Chem..

[11]  Guillermo Moyna,et al.  Shape signatures: a new approach to computer-aided ligand- and receptor-based drug design. , 2003, Journal of medicinal chemistry.

[12]  Matthias Keil,et al.  Pattern recognition strategies for molecular surfaces. II. Surface complementarity , 2002, J. Comput. Chem..

[13]  R Abagyan,et al.  The contour-buildup algorithm to calculate the analytical molecular surface. , 1996, Journal of structural biology.

[14]  Matthias Keil,et al.  Pattern recognition strategies for molecular surfaces. I. Pattern generation using fuzzy set theory , 2002, J. Comput. Chem..

[15]  G. S. Gill,et al.  Molecular surface point environments for virtual screening and the elucidation of binding patterns (MOLPRINT) , 2004 .

[16]  Lorenz M. Hilty,et al.  Environmental Informatics as a New Discipline of Applied Computer Science , 1995 .

[17]  W. Kabsch.  A discussion of the solution for the best rotation to relate two sets of vectors , 1978 .

[18]  Andreas Bender,et al.  Molecular surface point environments for virtual screening and the elucidation of binding patterns (MOLPRINT) , 2004, 2004 IEEE International Conference on Systems, Man and Cybernetics (IEEE Cat. No.04CH37583).

[19]  David A. Cosgrove,et al.  A novel method of aligning molecules by local surface shape similarity , 2000, J. Comput. Aided Mol. Des..

[20]  W. Todd Wipke,et al.  Quadratic Shape Descriptors. 1. Rapid Superposition of Dissimilar Molecules Using Geometrically Invariant Surface Descriptors , 2000, J. Chem. Inf. Comput. Sci..