Statistical Mechanics with Quantum Potentials Application to Host Gues

DESCRIPTION provided by applicant Host molecules such as cyclodextrins and cucurbiturils can andapos captureandapos smaller molecules and affect their physical and chemical behavior The stronger the host molecule holds onto i e binds its smaller andapos guestandapos the larger the effect ca be Host molecules themselves can also be chemically altered i e derivatized which can change how strongly they bind guest molecules as well as their own physical properties Scientists are discovering many human health related applications for host guest technology including improvement of the properties of drugs to make them more effective and safer potential scavengers for chemical warfare agent removal and clean up of environmental chemical pollutants The amount of basic research as well as applied industrial Randamp D in this area is expanding rapidly Given a particular andapos guestandapos molecule e g drug candidate chemical pollutant key pieces of information Randamp D scientists require is the host guest binding affinity and the association dissociation rates This SBIR project aims to develop a software tool that can accurately predict these host guest binding properties e g binding free energy This would allow Randamp D scientists to carry out computational experiments reducing the number of expensive and time consuming bench experiments required There is a current need for such a software tool to be developed because as recently demonstrated by a blinded test challenge existing tools are not accurate enough to provide useful information to researchers Very recent studies indicate that the accuracy of the predictions can be significantly improved by combining quantum mechanical QM energy functions with rigorous statistical mechanics However these proof of concept studies have yet to be translated into a robust computational tool suitable for applied Randamp D Therefore this project will interface VeraChemandapos s current statistical mechanics software package VM with the widely used quantum chemistry package GAMESS and implement drivers for various computational schemes to achieve this goal In this proposed hybrid methodology a Boltzmann distribution of molecular conformations will still be generated via a thorough conformational search as it is for classical VM however the conformational search will not solely rely on molecular mechanics but will be guided by the more reliable QM potential QM potentials will also be used for entropy terms including a treatment of anharmonic effects Full advantage will be taken of recent dramatic improvements in reliability of semi empirical QM SEQM with optional corrections at higher levels of QM Turnaround of calculations will be speeded up by parallel processing and a sophisticated conformer filter vetting process PUBLIC HEALTH RELEVANCE There are cage like molecules scientists call andapos hostsandapos which can capture smaller andapos guestandapos molecules and by holding onto them can alter their behavior in a way beneficial to human health The guest molecule could be a pharmaceutical drug environmental chemical pollutant or even a chemical warfare agent This project aims to develop a software tool that can predict how strongly a particular host molecule will hold onto a particular guest molecule thereby helping scientists design host molecules for use in human health related products and services