SHEF: a vHTS geometrical filter using coefficients of spherical harmonic molecular surfaces.
SHEF (spherical harmonic coefficient filter), a geometrical matching procedure constituting a preliminary step in the virtual high throughput screening of large databases of small drug-like molecules, is demonstrated. This filter uses a description of both the binding site of the target and the ligand surfaces using spherical harmonic polynomial expansions. Using this representation, which is based on limited sets of spherical harmonic coefficients, considerably reduces the complexity of surface complementarity calculation. As a first test, 188 known protein-ligand complexes were used, and the results of docking the abstracted ligands into the bare proteins using SHEF were compared to the original X-ray structures. The ability of SHEF to retrieve known ligands "hidden" in a virtual library of 1,000 randomly selected drug-like compounds is also demonstrated.
Cai
Wensheng
W
Department of Chemistry, Nankai University, Tianjin 300071, People's Republic of China. wscai@nankai.edu.cn
Xu
Jiawei
J
Shao
Xueguang
X
Leroux
Vincent
V
Beautrait
Alexandre
A
Maigret
Bernard
B
D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016333:HIV Protease / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D019151:Peptide Library; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000737:chemistry
D008024:Ligands; D019151:Peptide Library; D018167:Receptors, Calcitriol; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1