环氧合酶-2抑制剂设计中小分子构象与能量变化

目的 研究环氧合酶－2（COX－2）和配体复合物结构中药物小分子的能量及构象变化，为选择性COX－2抑制剂的研究奠定基础。方法 从PDB库中提取COX－2与选择性抑制剂（SC－588）作用复合物的X－线晶体结构，在由美国Tripos公司提供的Alchemy2000平台上，剥离与之结合的药物小分子SC－588，然后同孤立态优势构象进行能量及性质比较。结果 复合物晶体结构中药物分子的低能构象及其孤立态优势构象在能量和性质上均有差异。结论 分子活性构象并不一定是低能构象，其能量往往介于孤立态能量和复合物结合状态时最低能量之间，根据活性构象可设计新型药物分子。

Changes of small molecular energy and conformation in design of Cox-2-selective inhibitor

AIM To study the changes of small molecular energy and conformation in Cox 2 selective inhibitor design. METHODS Molecular structure of Cyclooxygenase 2 (COX 2) was found on the internet protein database and the file was dounloaded with the molecular coordinates for COX 2, and entered Alchemy 2000. The selective inhibitor (SC 558) was extracted completely from the SC 558/COX 2 complex. The static energy and molecular property were calculated in optimized and unoptimized conformations in an isolated situation. RESULTS Optimized conformation and isolated conformation were different in energy and property. CONCLUSION Molecular energy in active conformation usually is not the minimum energy, but between optimized and isolated situation. We may design the new molecule based upon the active conformations.