Many infectious diseases as well as cancers are strongly influenced by molecular level processes. In several cases, the advent of rapid genetic sequencing, already available in the case of HIV, means that patient-specific treatment based on genetic data becomes conceivable. Targeted therapies use drugs to interfere with specific biomacromolecules involved in disease development. Given the complexity of emergent mutations in such biomacromolecules and in the disease itself, clinicians need to resort to decision support software for patient-specific treatment. Incorporating model based molecular level information into such decision support systems offers the potential to substantially enhance personalised drug treatment by providing first principles based ranking of drug efficacy on a specific patient. Patient specific molecular models of targeted macromolecules are constructed and molecular dynamics simulations are used to rank drug binding affinities. Here we present results from clinically relevant protein variants that arise from two distinct pathologies: HIV and lung carcinoma. Our findings demonstrate the potential for molecular simulations to achieve an accurate ranking of drug binding affinities on clinically relevant time scales and represent the first steps towards the eventual goal of providing data derived from patient specific simulation to enhance clinical decision support systems. The approach gives rapid, robust, and accurate computational results and is dependent on an automated workflow for building, simulating and analysing models distributed over petascale computing resources which are comprised of tens to hundreds of thousands of compute cores.
Comments: 23 Pages.
[v1] 2012-09-04 05:55:45
Unique-IP document downloads: 94 times
Vixra.org is a pre-print repository rather than a journal. Articles hosted may not yet have been verified by peer-review and should be treated as preliminary. In particular, anything that appears to include financial or legal advice or proposed medical treatments should be treated with due caution. Vixra.org will not be responsible for any consequences of actions that result from any form of use of any documents on this website.
Add your own feedback and questions here:
You are equally welcome to be positive or negative about any paper but please be polite. If you are being critical you must mention at least one specific error, otherwise your comment will be deleted as unhelpful.