Li L, Darden T, Hiskey R, Pedersen L G
Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA.
Haemostasis. 1996;26 Suppl 1:54-9. doi: 10.1159/000217241.
We have employed molecular dynamics simulations to understand the properties of the gamma-carboxyglutamic acid (Gla) domains of human prothrombin fragment 1 (residues 1-144) and factor IX (residues 1-47). The simulations are based on (1) the crystal structure of bovine prothrombin fragment 1 in the presence of calcium and (2) our subsequent simulation of the solution structure for which we found accommodation of the long range ionic forces critical. In addition, we have estimated the solution structures for key mutant proteins [prothrombin (Gla6 to Asp and Gla16 to Asp) and factor IX (Gly12 to Ala)]. The simulations for the latter two mutants do not stabilize, a result in concert with the known biological data.
我们采用分子动力学模拟来了解人凝血酶原片段1（第1 - 144位氨基酸残基）和因子IX（第1 - 47位氨基酸残基）的γ-羧基谷氨酸（Gla）结构域的特性。这些模拟基于：（1）在钙离子存在下牛凝血酶原片段1的晶体结构；（2）我们随后对溶液结构的模拟，在此模拟中我们发现长程离子力的调节至关重要。此外，我们还估算了关键突变蛋白[凝血酶原（Gla6突变为Asp和Gla16突变为Asp）和因子IX（Gly12突变为Ala）]的溶液结构。对后两种突变体的模拟不稳定，这一结果与已知的生物学数据一致。
