Processes Underlying Interactions of Human Lactoferrin with the Jurkat Human Lymphoblastic T‐cell Line Receptor. II ‐ Comparative Molecular Field Analysis

It has previously been established that all or part of residues 4 ‐ 52 of human lactoferrin interact with the specific T‐lymphocyte receptor. Furthermore, the preliminary study using classical quantitative structure‐affinity relationships (QSAR) models have pointed out the importance of some H‐bond donor and acceptor groups of aminoacids in the interactions. In the present paper, comparative molecular field analysis (CoMFA) was used as a three‐dimensional QSAR method to define major steric and electrostatic features of lactoferrin‐T‐lymphocyte interactions. According to steric interaction energies, some residues of human lactoferrin: R3, F20, Q23, R24, S38 and Q47, previously described by the QSAR method, as well as Q21, R27 and R56 look essential for interactions. The results of the electrostatic features study are also in good agreement with the QSAR H‐bonds model and demonstrate that the pHi is a significant binding factor. Taken as a whole, QSAR and CoMFA methods allow to define two regions, potentially involved in selectivity between species, R3, Q7, N13, Q23, R24, S38, Q50 and N55; and binding potency, P14, F20, D43, S44, P45 and Q47.