Liwo A, Ołdziej S, Kaźmierkiewicz R, Groth M, Czaplewski C
Department of Chemistry, University of Gdańsk, Poland.
Acta Biochim Pol. 1997;44(3):527-47.
Prediction of protein structure from amino-acid sequence still continues to be an unsolved problem of theoretical molecular biology. One approach to solve it is to construct an appropriate (free) energy function that recognizes the native structures of some selected proteins (whose native structures are known) as the ones distinctively lowest in (free) energy and then to carry out a search of the lowest-energy structure of a new protein. In order to reduce the complexity of the problem and the cost of energy evaluation, the so-called united-residue representation of the polypeptide chain is often applied, in which each amino-acid residue is represented by only a few interaction sites. Once the global energy minimum of the simplified chain has been found, the all-atom structure can easily and reliably be constructed. The search of the lowest-energy structure is usually carried out by means of Monte Carlo methods, though use of more efficient global-optimization methods, especially those of deformation of original energy surface is potentially promising. Monte Carlo search of the conformational space can be accelerated greatly, if the chain is superposed on a discrete lattice (the on-lattice approach). On the other hand, the on-lattice approach prohibits the use of many efficient global-optimization methods, because they require both energy and its space derivatives. The on-lattice methods in which the chain is embedded in the continuous 3D space are, therefore, also worth developing. In this paper we summarize the work on the design and implementation of an off-lattice united-residue force field that is underway in our group, in cooperation with Professor HA. Scheraga of Cornell University, U.S.A.
从氨基酸序列预测蛋白质结构仍然是理论分子生物学中一个尚未解决的问题。解决这个问题的一种方法是构建一个合适的（自由）能函数，该函数将一些选定蛋白质（其天然结构已知）的天然结构识别为（自由）能明显最低的结构，然后搜索新蛋白质的最低能量结构。为了降低问题的复杂性和能量评估成本，通常采用多肽链的所谓统一残基表示法，其中每个氨基酸残基仅由几个相互作用位点表示。一旦找到简化链的全局能量最小值，就可以轻松可靠地构建全原子结构。最低能量结构的搜索通常通过蒙特卡罗方法进行，不过使用更高效的全局优化方法，尤其是那些对原始能量表面进行变形的方法，可能很有前景。如果将链叠加在离散晶格上（晶格方法），蒙特卡罗对构象空间的搜索可以大大加速。另一方面，晶格方法禁止使用许多高效的全局优化方法，因为它们需要能量及其空间导数。因此，将链嵌入连续三维空间的非晶格方法也值得开发。在本文中，我们总结了我们小组与美国康奈尔大学的HA. Scheraga教授合作正在进行的关于非晶格统一残基力场的设计和实现的工作。
