Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins

Abstract

The structures of proteins are well-packed, yet they contain numerous cavities which play key roles in accommodating small molecules, or enabling conformational changes. From high-resolution structures it is possible to identify these cavities. We have developed a precise algorithm based on alpha shapes for measuring space-filling-based molecular models (such as van der Waals, solvent accessible, and molecular surface descriptions). We applied this method for accurate computation of the surface area and volume of cavities in several proteins. In addition, all of the atoms/residues lining the cavities are identified. We use this method to study the structure and the stability of proteins, as well as to locate cavities that could contain structural water molecules in the proton transport pathway in the membrane protein bacteriorhodopsin.

Structural Rigidity of a Large Cavity-containing Protein Revealed by High-pressure Crystallography

“…All volume calculations reported here are made with the program VOLBL, described by Liang et al 44,45 This program uses the so-called alpha-shape formalism, 11,12 which is similar to Voronoi decomposition, but overcomes some difficulties, particularly in defining the molecular envelope.…”

Computational analysis of ligand binding dynamics at the intermolecular hot spots with the aid of simulated tempering and binding free energy calculations

“…The bulk of the ligand-protein interactions is determined by the appropriate positioning of the benzimidazole core motif in place of mutated W104 residue. The total electrostatics contribution is mildly destabilizing for the majority of the inhibitors, except the most potent E8 ligand, where the electrostatic intermolecular interactions are not fully offset by the unfavorable polar solvation [92][93][94][95].…”

CAVE: A package for detection and quantitative analysis of internal cavities in a system of overlapping balls: Application to proteins

“…The energetics of the empty cavities and internal mutations have been evaluated computationally in [30]. Liang, et al [31] described an analytic method for computing the metric properties of macromolecules. Later this method has been applied to study quantitatively the inaccessible cavities in proteins [32].…”

“…Liang, et al [31] described an analytic method for computing the metric properties of macromolecules. Later this method has been applied to study quantitatively the inaccessible cavities in proteins [32]. Another analytical algorithm has been suggested in [33].…”