ABSTRACT:The 3D structure determination of a protein is crucial for structure-guided drug development and the homology modeling approach is the most accurate method among the computational methods, yielding reliable models. Loop predictions are required in many protein homology modeling studies and raise the problem of loop closure. Loop closure problems have been solved mainly by “ab-initio” methods or by employing databases. “ab-initio” methods mostly use standard bond lengths and angles. However, backbone bonds and angles are not standard in different crystallographic structures, thus, is it possible to achieve high quality loop closure by employing standard bond lengths and angles? To explore this issue we reconstructed loops from the structurally refined proteins with standard parameters but retained the experimental backbone dihedral angles. This was tested by stepwise construction from one of the terminals (N- and C-) toward the other as well as from both terminals towards the center. We conclude that introducing variability for bond lengths, for bond angles and for omega dihedrals, is essential for accurate prediction of loops. As well, constructing loops from both terminals toward the center give more precise models, closer to native structures.
ABSTRACT:Phylogenetic analysis of the mammalian and avian polyomaviruses was performed using the most complete set of publicly available polyomavirus genome sequences to date, including the newly discovered MW polyomavirus. There is no evidence for host-switching between mammalian and avian polyomaviruses, but there is extensive evidence for host-switching among mammalian polyomaviruses. Comparative genomic analysis focuses on primate polyomaviruses, and two specific genomic alterations are shown for Merkel cell polyomavirus and Trichodysplasia spinulosa-associated polyomavirus that may indicate a mechanism for primate host-switching for these two human polyomaviruses.
KeyWords: PyV = polyomavirus, LCA= last common ancestor.
How to cite: Warden CD and Lacey SF J. Bioinfo. Res. 1(4) 2012: 46-49
Warden CD and Lacey SF J. Bioinfo. Res. 1(4) 2012: 46-49
ABSTRACT:Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome. HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that copies the RNA genome of HIV-1 into DNA. The dipyridodiazepinone Nevirapine is a potent and highly specific inhibitor of the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1). It is a member of an important class of non-nucleoside drugs. In this paper, we report virtual screening analysis of HIV-RT from PDB database versus chemical compounds from ZINC database using eHiTS software. Using molecular constraint search, 884 ligands were extracted and docking analysis resulted in 59 best hits. Based on binding compatibilities with receptor, top three molecules (ZINC04923148, ZINC05442451 and ZINC04923002) were reported as possible novel HIV-RT inhibitors.
KeyWords: HIV reverse transcriptase, virtual screening, ZINC database, ehits, docking.
How to cite: PVRD Prasada Rao and A Govardhan J. Bioinfo. Res. 1(4) 2012: 50-54