SBIR-STTR Award

This is an application to develop a scalable computational infrastructure to enable virtual screening of chemical libraries using the Amazon EC2 cloud computing environment and automated docking tools. Structure-based virtual screening is an important tool in the drug discovery process (1-7). The use of computational tools has allowed for the screening of large libraries of chemical compounds to identify putative ligand-receptor interactions (8-9). The identification of valid targets and therapeutic compounds has long-term importance both to the public health and the economic strength of the pharmaceutical industry. Receptor-based virtual screening (VS) is a technique in which computational tools are used dock small molecular weight compounds into a protein receptor or enzyme. This technique is most often used in drug discovery, where a large library of chemical structure can be docked and scored to assess the potential if a compound to bind to a drug target. However, high-throughput virtual screening is computationally intensive, and the cost of building, maintaining, and managing a dedicated computing cluster limits access to these technologies to large universities and commercial enterprises. Internet-based computing, also known as cloud computing, is a business service model in which computational resources are accessed on-demand as needed, and is affordable, scalable, and secure. We have utilized the Amazon EC2 cloud computing environment for virtual screening of chemical libraries of 100 to 10000 compounds against two targets of therapeutic interest. This application will further expand the capacity for virtual screening by: (1) development of the software infrastructure required for computational cluster virtualization and management;(2) development of a basic user interface for submission and management of virtual screening requests and evaluation of results;(3) validation of this approach through analysis of screening results with our collaborators. The test of this platform will be focused on function and utility: (1) demonstrate the ability to screen a library of 1.4 million to 2.0 million compounds against known therapeutic targets;(2) comparison of performance against a dedicated cluster using equivalent docking software, chemical libraries, and targets;(3) ability to utilize the web interface to conduct virtual screens.

Public Health Relevance:
The Phase I SBIR project ""Application of Cloud Computing Resources for Virtual Screening"" will deliver new technologies for the structure-based identification of small molecule ligands of proteins and enzymes. By significantly increasing the ability of researchers to access tools for in-silico screening, we will facilitate identification of novel therapeutic compounds used in the treatment of disease, and thereby improving the public health.

Thesaurus Terms:
Access To Care;Access To Health Care;Access To Healthcare;Accessibility Of Health Care;Availability Of Health Services;Back;Binding;Binding (Molecular Function);Businesses;Chemical Structure;Computer Models;Computer Simulation;Computer Software Tools;Computer Based Simulation;Computer Software;Computerized Models;Data;Data Banks;Data Bases;Databanks;Databases;Development;Disease;Disorder;Docking;Dorsum;Drug Delivery;Drug Delivery Systems;Drug Industry;Drug Targeting;Electronic Databank;Electronic Database;Environment;Enzymes;Equilibrium;Evaluation;Goals;Health Services Accessibility;Infrastructure;Internet;Investigators;Jobs;Loinc Axis 4 System;Learning;Libraries;Ligands;Linux;Mathematical Model Simulation;Mathematical Models And Simulations;Modeling;Molecular Interaction;Molecular Weight;Occupations;Outcome;Performance;Pharmaceutic Industry;Pharmaceutical Industry;Phase;Preparation;Process;Professional Postions;Proteins;Public Health;Publishing;Receptor Protein;Research;Research Infrastructure;Research Personnel;Research Resources;Researchers;Resources;Sbir;Sbirs (R43/44);Schedule;Screening Result;Screening Procedure;Secure;Services;Small Business Innovation Research;Small Business Innovation Research Grant;Software;Software Tools;Sorting - Cell Movement;Structure;System;Techniques;Technology;Testing;Timeline;Universities;Validation;Www;Work;Zinc;Zn Element;Access To Health Services;Access To Services;Access To Treatment;Availability Of Services;Balance;Balance Function;Base;Care Access;Chemical Library;Clinical Data Repository;Cluster Computing;Computational Grid;Computational Infrastructure;Computational Modeling;Computational Models;Computational Resources;Computational Simulation;Computational Tools;Computer Based Models;Computer Infrastructure;Computer Program/Software;Computerized Modeling;Computerized Simulation;Computerized Tools;Computing Resources;Cost;Cost Effective;Cost-Effective;Data Grid;Data Repository;Datagrid;Develop Software;Developing Computer Software;Developmental;Disease/Disorder;Distributed Computing;Drug Discovery;Gene Product;Grid Computing;Health Care Availability;Health Care Service Access;Health Care Service Availability;Health Economics;Health Services Availability;Healthcare Access Availability;Healthcare Service Access;Healthcare Service Availability;Improved;In Silico;Interest;Middleware;New Technology;New Therapeutics;Next Generation Therapeutics;Novel Technologies;Novel Therapeutics;Programs;Public Health Medicine (Field);Receptor;Screening;Screenings;Small Molecule;Small Molecule Libraries;Software Development;Sorting;Therapeutic Target;Tool;Tool Development;Virtual;Virtual Simulation;Web;Web Interface;Web Services;World Wide Web

This is a Phase II application for continued development of the Chemalytics Platform, a scalable computational infrastructure to enable virtual screening of chemical libraries using the Amazon EC2 cloud computing environment and automated docking tools. Structure-based virtual screening is an important tool in the drug discovery process (1-7). The use of computational tools has allowed for the screening of large libraries of chemical compounds to identify putative ligand-receptor interactions (8-9). The identification of valid targets and therapeutic compounds has long-term importance both to the public health and the economic strength of the pharmaceutical industry. Receptor-based virtual screening (VS) is a technique in which computational tools are used dock small molecular weight compounds into a protein receptor or enzyme. This technique is most often used in drug discovery, where a large library of chemical structure can be docked and scored to assess the potential if a compound to bind to a drug target. However, high-throughput virtual screening is computationally intensive, and the cost of building, maintaining, and managing a dedicated computing cluster limits access to these technologies to large universities and commercial enterprises. Internet-based computing, also known as cloud computing, is a business service model in which computational resources are accessed on-demand as needed, and is affordable, scalable, and secure. We have completed the Phase I goals of a building a web-based interface to manage users, jobs, and display results from virtual docking screens. The current system employs the Amazon EC2 environment and has been successfully used to screen chemical libraries of more than 2.3 million structures in an economical and rapid fashion. In collaboration with a biotechnology partner, we are now pursuing chemical leads which are active against prostate cancer cell lines. In this phase we will expand the capabilities of the current system through the following technical achievements: (1) integration of additional chemical libraries and library filtering tools to focus search space prior to docking; (2) enhancement of end user ability to evaluate results through integration of data analysis and visualization tools; (3) validation of this approach through analysis of screening results with our collaborators and commercial partners.

Public Health Relevance Statement:


Public Health Relevance:
The Phase II SBIR project "Application of Cloud Computing Resources for Virtual Screening" will build upon the existing Chemalytics cloud computing platform, which provides screening tools to identify drug candidates against biological targets using public or proprietary chemical libraries. The major advantages of this web-based platform are its low cost and ease of use compared to existing high-throughput virtual screening applications. By significantly increasing the ability of researchers to access tools for in-silico screening, we will facilitate identification of novel therapeutic compounds used in the treatment of disease, and thereby improving the public health.

Project Terms:
Achievement; Algorithms; analytical tool; Back; base; Binding (Molecular Function); Binding Sites; Biological; Biotechnology; Businesses; chemical property; Chemical Structure; Chemicals; Client; Cloud Computing; cluster computing; Collaborations; computer infrastructure; Computer Simulation; Computer software; computerized tools; computing resources; cost; cost effective; Data Analyses; Databases; Development; Disease; Docking; drug candidate; drug discovery; Drug Industry; Drug Targeting; encryption; Environment; Enzymes; Evaluation; Goals; health economics; Housing; Imagery; improved; Informatics; Internet; Learning; Libraries; Ligands; macromolecule; Mediation; Modeling; Modification; Molecular Weight; Nature; novel therapeutics; Occupations; Online Systems; Outcome; PC3 cell line; Performance; Phase; Process; Property; public health medicine (field); public health relevance; receptor; Research; Research Infrastructure; Research Personnel; screening; Screening Result; Secure; Security; Security Measures; Services; Small Business Innovation Research Grant; small molecule libraries; Specific qualifier value; Staging; Structure; System; Techniques; Technology; Testing; therapeutic target; TimeLine; tool; Universities; Validation; Vendor; virtual; web based interface; web interface; web services; Work