title: Analysis of structural water and CH···π interactions in HIV-1 protease and PTP1B complexes using a hydrogen bond prediction tool, HBPredicT.
abstract: A hydrogen bond prediction tool HBPredicT is developed for detecting structural water molecules and CH···π interactions in PDB files of protein-ligand complexes. The program adds the missing hydrogen atoms to the protein, ligands, and oxygen atoms of water molecules and subsequently all the hydrogen bonds in the complex are located using specific geometrical criteria. Hydrogen bonds are classified into various types based on (i) donor and acceptor atoms, and interactions such as (ii) protein-protein, (iii) protein-ligand, (iv) protein-water, (v) ligand-water, (vi) water-water, and (vii) protein-water-ligand. Using the information in category (vii), the water molecules which form hydrogen bonds with the ligand and the protein simultaneously-the structural water-is identified and retrieved along with the associated ligand and protein residues. For CH···π interactions, the relevant portions of the corresponding structures are also extracted in the output. The application potential of this program is tested using 19 HIV-1 protease and 11 PTP1B inhibitor complexes. All the systems showed presence of structural water molecules and in several cases, the CH···π interaction between ligand and protein are detected. A rare occurrence of CH···π interactions emanating from both faces of a phenyl ring of the inhibitor is identified in HIV-1 protease 1D4L.
authors.affiliation: Computational Modeling and Simulation Section, National Institute for Interdisciplinary Science and Technology (CSIR), Trivandrum, India.
authors.forename: Joshy P
authors.initials: JP
authors.lastname: Yesudas
authors.forename: Fareed Bhasha
authors.initials: FB
authors.lastname: Sayyed
authors.forename: Cherumuttathu H
authors.initials: CH
authors.lastname: Suresh
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D055808:Drug Discovery; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000737:chemistry* / Q000378:metabolism*; D012984:Software; D014867:Water / Q000737:chemistry*
chemical_list: D008024:Ligands; D014867:Water; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1