Automated protein motif generation in the structure-based protein function prediction tool ProMOL

Abstract

ProMOL, a plugin for the PyMOL molecular graphics system, is a structure-based protein function prediction tool. ProMOL includes a set of routines for building motif templates that are used for screening query structures for enzyme active sites. Previously, each motif template was generated manually and required supervision in the optimization of parameters for sensitivity and selectivity. We developed an algorithm and workflow for the automation of motif building and testing routines in ProMOL. The algorithm uses a set of empirically derived parameters for optimization and requires little user intervention. The automated motif generation algorithm was first tested in a performance comparison with a set of manually generated motifs based on identical active sites from the same 112 PDB entries. The two sets of motifs were equally effective in identifying alignments with homologs and in rejecting alignments with unrelated structures. A second set of 296 active site motifs were generated automatically, based on Catalytic Site Atlas entries with literature citations, as an expansion of the library of existing manually generated motif templates. The new motif templates exhibited comparable performance to the existing ones in terms of hit rates against native structures, homologs with the same EC and Pfam designations, and randomly selected unrelated structures with a different EC designation at the first EC digit, as well as in terms of RMSD values obtained from local structural alignments of motifs and query structures. This research is supported by NIH grant GM078077.

Mad1 destabilizes p53 by preventing PML from sequestering MDM2

“…The SIM consists of a hydrophobic core separated from an acidic stretch by a short spacer region 46,47 . Structural analysis and visualization of the Mad1 CTD using SWISS-MODEL Workspace (4dzo.1) and PyMOL software 48 , revealed a hydrophobic surface localized within the putative SIM at aa 689–692 (Supplementary Fig. 3a).…”

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

“…Thus, we determined whether negatively charged myricetin attenuates the interaction of SEVI with HIV-1 virions by affecting the cationic properties of SEVI fibrils. Zeta potential is commonly employed to quantitate the magnitude of charge of materials; such charge is an important indicator of the stability and degree of electrostatic repulsion of colloidal dispersions [ 31 , 32 ]. Myricetin significantly decreased the zeta potential of SEVI fibrils in a dose-dependent manner (Fig.…”

“…Hydrogen atoms were added using the Dock Prep module. The protein–ligand interaction online analysis tool Protein–Ligand Interaction Profiler [ 59 ] was applied, and images were generated by PyMOL software [ 31 ].…”

“…The inhibitory activity of myricetin and other ARV drugs and combinations on infection by HIV-1 SF162 infectious clones was determined as previously described [ 30 , 31 , 61 ]. Briefly, HIV-1 SF162 at 100 TCID 50 (50% tissue culture infective dose) was incubated in the presence or absence of various concentrations of myricetin, ARV drugs or combinations thereof in SE-F at 37 °C for 30 min.…”

Molecular docking based virtual screening of the breast cancer target NUDT5

“…The docking of the ligand 7-[[5-(3, 4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methyl]-1,3-dimethyl-8-piperazin-1-yl-purine-2,6-dione with theNUDT5 protein was done as described elsewhere [29] and their interaction featured were calculated using PyMOL [30] to assess docking efficiency.…”