The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α(1)-antitrypsin (A1AT). Pathological mutations disturb the conformation...

Objective: Traditional medicine is often considered to be a kind of complementary or alternative (CAM) nowadays. Therefore, documenting and identifying the herbs that are effective in treating various diseases vital for future disease control programs. This study aims perform molecular docking analysis thirteen plant components Bauhinia acuminata against target proteins lung cancer (PDB IDs: 2I...

Pyruvate-ferredoxin oxidoreductatse (PFOR) carries out the central step in oxidative decarboxylation of pyruvate to acetyl-CoA. We have purified this enzyme from Desulfovibrio vulgaris Hildenborough (DvH) as part of a systematic characterization of as many multiprotein complexes as possible for this organism, and the three-dimensional structure of this enzyme has been determined by a combinatio...

In cardiovascular system, activation of Endothelin receptors causes vasoconstriction which leads to Pulmonary Arterial Hypertension (PAH). Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension. Bosentan is intended to affect vasoconstriction, hypertrophic and fibrotic effects by blocking the actions of receptors ET(A) and ET(B). In th...

The main functional components of green tea, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), are found to have a broad antineoplastic activity. The discovery of their targets plays an important role in revealing the antineoplastic mechanism. Therefore, to identify potential target proteins for tea polyphenols, we have taken a comp...

A new approach is presented that combines structure- and ligand-based virtual screening in a reverse way. Opposite to the majority of the methods, a docking protocol is first employed to prioritize small ligands ("fragments") that are subsequently used as queries to search for similar larger ligands in a database. For a given chemical library, a three-step strategy is followed consisting of (1)...

Alzheimer's disease is a multifactorial neurodegenerative disorder with many drug targets contributing to its etiology. Despite the devastating effects of this disease, therapeutic methods for treating Alzheimer's disease remain limited. The multifactorial nature of Alzheimer's disease strongly supports a multi-target rationale as a drug design strategy. Glycogen synthase kinase-3 beta and cycl...

We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD) simulations and free energy calculations. To test the effectiveness of MolGridCa...

In this paper we describe the search strategies developed for docking flexible molecules to macomolecular sites that are incorporated into the widely distributed DOCK software, version 4.0. The search strategies include incremental construction and random conformation search and utilize the existing Coulombic and Lennard-Jones grid-based scoring function. The incremental construction strategy i...

in this paper we address the vrpcd, in which a set of homogeneous vehicles are used to transport products from the suppliers to customers via a cross-dock. the products can be consolidated at the cross-dock but cannot be stored for very long as the cross-dock does not have long-term inventory-holding capabilities. the objective of the vrpcd is to minimize the total traveled distance while respe...