bmdo technologies for biomedical applications - MDA Technology

HIGH-SPEEDMOLECULAR MODELING• Molecular modeling can greatlyspeed up decision making in drugselection strategy.BMDO HISTORYWith the help of BMDO contracts to simulate the mechanical behavior oflarge space-based structures, Photon Research Associates (PRA; San Diego,CA) has developed a computer algorithm that reduces the time needed tomodel the dynamics of large molecular systems. In the early to mid-1980s,PRA developed multibody modeling technology to simulate the dynamics oflarge space-based structures. The originalsponsors of this research included theIn the immune system,Defense Advanced Research Projects Agencyand NASA. Tests of the algorithm, calledthe shape of an invadingMBO(N)D, have shown that it can simulatepathogen and thethe dynamics of large molecules (10,000atoms) up to 50 times faster than conventionalall-atom modeling techniques, while“memory” of the immunemaintaining accuracy in the essential dynamics.Applications to larger molecules (10,000system for this shapeto 100,000 atoms) and further refinementshelp dictate whether ato the algorithm should make it about 100 to1,000 times faster than all-atom approaches.person acquires anHOW IT WORKSinfection, fights off theMBO(N)D accelerates computational speedwhile maintaining a great deal of chemicalinfection, or developsand physical realism. This achievement isan autoimmune disease. possible through a technique known as “substructuring,”which combines atoms intointeracting groups of rigid and flexible bodies.The algorithm also filters out high-frequency motions that do not affectthe overall behavior of the molecule. These two innovations reduce the numberof system variables and allow the simulation to be computed over asmaller number of time steps.38MEDICAL SIGNIFICANCEDrug discovery has changed over the past 15 years to include the study ofsignificant structural components in and around the cell. Molecular structuresof proteins and receptor-ligand complexes play an important role inthe discovery of novel agents. A ligand is a biological compound that fits areceptor within or on the cell surface in a “lock and key” arrangement.Drugs that mimic the shape of the natural ligand can be used to up- ordown-regulate a signal that is transduced by the cell receptor. Some receptorstructures are found by x-ray crystallography, some by nuclear magneticresonance, and some by homologous comparisons to similar structures.All of these techniques rely on molecular dynamics to find the correctpositions of all the atoms in the drug and the receptor and how theymove to interact with each other. While highly parallel supercomputersChapter 2 - Observation TechnologiesSection B - AnalysisBMDO Technologies for Biomedical Applications