ZDOCK Server Research Articles

Enhanced Interaction of Shuffled Mutacin IV, an Antimicrobial Peptide of Bacterial Origin, with Surface Protein IsdB of Staphylococcus aureus

Antimicrobial peptides are produced by prokaryotes and eukaryotes with fundamental role of protection against pathogenic microbes. Staphylococcus aureus, a major virulent pathogen in humans, shows multiple drug resistance and is affected by the bacteriocin activity of Mutacin IV. Currently, peptide therapeutics has been reported as a potential alternative for treating microbial infections specially exhibiting multiple drug resistance. However, the mechanism of action and interaction of peptides with target proteins is not known. The current work is an attempt to address the above issue by performing molecular docking and randomization experiments. In this study, antimicrobial peptides of bacterial origin (168 peptides) were collected from APD2 database and their net charge and hydrophobicity values were retrieved. Mutacin IV (APD Id—AP01174), a 44 amino acids long peptide derived from Streptococcus mutans UA140, was selected on the basis of high hydrophobicity to net charge ratio (0.52) and used for in silico docking studies with therapeutically important surface proteins viz. IsdA, IsdB, ClfB, and SasG of S. aureus using ZDOCK server. The docking result of IsdB surface protein and Mutacin IV was found better (ZDOCK score 1168.582) as compared to others. Afterwards, the native Mutacin IV sequence was randomized to generate 50 new combinations using EMBOSS (Shuffleseq) tool. The new sequence of Mutacin IV was screened on the basis of high in vivo to in vitro aggregation ratio (i.e. high in vivo aggregation and low in vitro aggregation values) and good binding energies against IsdB surface protein of S. aureus from the randomized sequences. The new peptide sequence showed an in vivo to in vitro aggregation ratio of 2.206 and 0.888, respectively which is higher than native sequence of Mutacin IV ratio (0.205). Moreover, the ZDOCK scores were found to be 1370.529 and 1687.048 which were better than the native sequence of Mutacin IV (ZDOCK score 1168.582). This research work identifies the new sequence of Mutacin IV peptide which binds effectively to the surface proteins of S. aureus and thereby could be a better peptide than native Mutacin IV. Our finding also demonstrates enhanced interactions of new Mutacin IV peptide with IsdB surface protein to understand the structural implications and proposes its effective antimicrobial role against S. aureus.

In-silico comparative study of inhibitory mechanism of Plant Serine Proteinase Inhibitors.

The nematodes like root-knot and cyst are plant-parasitic pest found in horticultural and agricultural crops. They do damages in the roots of plants as a result losses million tons of production. High cost of nematicides and environment safety concern has necessitated finding of some alternative methods. Under Integrated Pest Management (IPM) such problems are solving significantly by means of target gene inhibition, agrobacterium mediated transformation etc. One of this strategy use Plant Proteinase Inhibitors (PIs) gene which are used to control the proteolysis mechanism of Pest by inhibiting gut Serine Proteinase (SP). Present work investigates the utility of computer aided methods to study the mechanism of Protein-Protein interactions and thereby inhibition of Serine Proteinase by PIs. Hence 3D models of Serine Proteinase as well as Serine Proteinase Inhibitors (SPIs) generated using homology modeling. Validations of constructed models have been done by PROCHECK, VERIFY3D, ERRAT and PROSA. Prediction of Protein interacting surface patches and site specific protein docking was performed by using ZDOCK Server. Backbone refinement of output protein complexes was executed in Fiber Dock server. Interaction study between SP and SPIs complexes shows their comparative inhibition efficacy, measured in terms of number of hydrogen bonds, Van dar wall attraction and docking energy. This work reported that Vigna marina and Phaseolus oligospermus are having better inhibition efficiency in comparison to other inhibitors.