Pharmit: interactive exploration of chemical space

Abstract

Pharmit (http://pharmit.csb.pitt.edu) provides an online, interactive environment for the virtual screening of large compound databases using pharmacophores, molecular shape and energy minimization. Users can import, create and edit virtual screening queries in an interactive browser-based interface. Queries are specified in terms of a pharmacophore, a spatial arrangement of the essential features of an interaction, and molecular shape. Search results can be further ranked and filtered using energy minimization. In addition to a number of pre-built databases of popular compound libraries, users may submit their own compound libraries for screening. Pharmit uses state-of-the-art sub-linear algorithms to provide interactive screening of millions of compounds. Queries typically take a few seconds to a few minutes depending on their complexity. This allows users to iteratively refine their search during a single session. The easy access to large chemical datasets provided by Pharmit simplifies and accelerates structure-based drug design. Pharmit is available under a dual BSD/GPL open-source license.

In SilicoIdentification of Novel PrfA Inhibitors to Fight Listeriosis: A Virtual Screening and Molecular Dynamics Studies

“…Pharmacophore models were developed using USR-VS (http://usr.marseille.inserm.fr/) [25] and PHARMIT (http://pharmit.csb.pitt.edu/) [26] web servers. These models were then used to perform LBVS.…”

Open source molecular modeling

“…Pharmit [156] is a successor of Pharmer that also incorporates shape matching and energy minimization (if a receptor structure is available) as part of the screen. It is primarily intended to be used as a backend to a web service.…”

Pharmacophore modeling, virtual computational screening and biological evaluation studies

“…We defined a new computational strategy protocol characterized by the use of bioinformatics online tools and by the application of locally installed tools, for lead candidates generationoptimization able to reduce the cycle time and cost of this process and to promote the next steps of study [2].…”

“…An alternative promising and efficient used to identify new active substances is Pharmacophore modeling method.We defined a new computational strategy protocol characterized by the use of bioinformatics online tools and by the application of locally installed tools, for lead candidates generation-optimization able to reduce the cycle time and cost of this process and to promote the next steps of study [2].Hence, we have tried to apply this new computational procedure, in a more detailed screening, of small bioactive molecules, searching and identifying new candidates as "lead compounds", potentially able to inhibit biological target AKT1 human protein and its related molecular mechanisms [3].The workflow executed in our work has been characterized by a multi-step design, which concerns different topics: search in PDB database of a model structure for AKT1, pharmacophore modeling and virtual computational screening, biological evaluation divided in two parts (molecular validation of selected compounds and study of physical-chemical properties related to pharmacokinetic/pharmacodynamics prediction models). All these step have been performed through PHARMIT (http://pharmit.csb.pitt.edu) and Discovery Studio 4.5 platform.We selected the PDB structure 3O96 as the reference complex (protein-ligand), and we analyzed it by means of PHARMIT and Discovery Studio, to generate four different "pharmacophore models" with four different list of natural compounds.It is performed a thorough screening of compounds applying several filters, to find some good candidates as possible natural AKT1 allosteric inhibitors.The compounds that match a well-defined pharmacophore have been analyzed through direct molecular docking, for selecting only the best candidates and studying the protein-ligand interactions.…”