Conformational transition pathways explored by Monte Carlo simulation integrated with collective modes
Biophysical Journal, cilt.95, sa.12, ss.5862-5873, 2008 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 95 Sayı: 12
- Basım Tarihi: 2008
- Doi Numarası: 10.1529/biophysj.107.128447
- Dergi Adı: Biophysical Journal
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.5862-5873
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Conformational transitions between open/closed or free/bound states in proteins possess functional importance. We propose a technique in which the collective modes obtained from an anisotropic network model (ANM) are used in conjunction with a Monte Carlo (MC) simulation approach, to investigate conformational transition pathways and pathway intermediates. The ANM-MC technique is applied to adenylate kinase (AK) and hemoglobin. The iterative method, in which normal modes are continuously updated during the simulation, proves successful in accomplishing the transition between open-closed conformations of AK and tense-relaxed forms of hemoglobin (Cα - root mean square deviations between two end structures of 7.13 Å and 3.55 Å, respectively). Target conformations are reached by root mean-square deviations of 2.27 Å and 1.90 Å for AK and hemoglobin, respectively. The intermediate conformations overlap with crystal structures from the AK family within a 3.0-Å root mean-square deviation. In the case of hemoglobin, the transition of tense-to-relaxed passes through the relaxed state. In both cases, the lowest-frequency modes are effective during transitions. The targeted Monte Carlo approach is used without the application of collective modes. Both the ANM-MC and targeted Monte Carlo techniques can explore sequences of events in transition pathways with an efficient yet realistic conformational search. © 2008 by the Biophysical Society.