title: SHEF: a vHTS geometrical filter using coefficients of spherical harmonic molecular surfaces.
abstract: 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.
authors.affiliation: Department of Chemistry, Nankai University, Tianjin 300071, People's Republic of China. wscai@nankai.edu.cn
authors.forename: Wensheng
authors.initials: W
authors.lastname: Cai
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xu
authors.forename: Xueguang
authors.initials: X
authors.lastname: Shao
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroux
authors.forename: Alexandre
authors.initials: A
authors.lastname: Beautrait
authors.forename: Bernard
authors.initials: B
authors.lastname: Maigret
mesh_terms: 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
chemical_list: D008024:Ligands; D019151:Peptide Library; D018167:Receptors, Calcitriol; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1