DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在过去几年中，我们一直在开发一个统一的残余力场UNRES。UNRES力场被推导为联合残基链的平均力的势，并最终基于分层蛋白质能量景观的概念进行参数化。在1998年、2000年、2002年和2004年对已知蛋白质进行的广泛测试和CASP 3、CASP 4、CASP 5和CASP 6的四次盲预测实验中，蛋白质结构预测得到了证实。最近我们在分子动力学中实现了UNRES力场。UNRES分子动力学运行的初步结果表明，我们能够模拟发生在微秒甚至毫秒时间尺度上的折叠事件。我们在2006年4月至2007年3月期间的研究计划是：i）继续开发UNRES力场的分子动力学代码; ii）继续使用经修订的分级势函数优化协议对UNRES力场进行微调; iii）增强UNRES力场的不同全球搜索方法的能力; iv）参与CASP 7演习。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. For the past several years, we have been developing a united residue force field UNRES. The UNRES force field has been derived as a potential of mean force of the united-residue chain and ultimately parameterized based on the concept of a hierarchical protein energy landscape. Protein structure prediction was demonstrated in extensive tests on known proteins and in four blind-prediction experiments CASP3, CASP4, CASP5, and CASP6 in years 1998, 2000, 2002, and 2004. Recently we implemented the UNRES force field in molecular dynamics. Initial results from UNRES molecular dynamics runs shows that we are able to simulate folding events which take place in a microsecond- or even a millisecond-time scale. Our research plan for the period APR/2006-MAR/2007 are: i) continuation of development of the molecular dynamics code for the UNRES force field; ii) continuation of the fine-tuning of the UNRES force field using a revised hierarchical potential-function optimization protocol; iii) enhancement of the capability of different global search methods for the UNRES force field; iv) participation in CASP7 exercise.