𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Investigation of the binding specificity of Erbin-PDZ affinity clamp by molecular dynamics simulations

✍ Scribed by Shulin Zhuang; Weiping Liu

Publisher
Elsevier
Year
2011
Tongue
English
Weight
810 KB
Volume
963
Category
Article
ISSN
2210-271X

No coin nor oath required. For personal study only.

✦ Synopsis

An exquisitely specific ''affinity clamp'' with nanomolar affinities was recently engineered via directed evolution strategy, which is composed of the human Erbin-PDZ domain and the fibronectin type III (FN3) domain. This high-specificity affinity clamp showed distinct binding affinity to two p120-related catenin peptides, d-catenin and ARVCF. To investigate the interactions between the affinity clamp and these two peptides and probe the ligand binding specificity, here we performed the molecular dynamics (MD) simulations and free energy evaluations on the complexes. A hydrogen bond network was discovered between ligands d-catenin, ARVCF and the affinity clamp. Compared with d-catenin, ARVCF formed more hydrogen bonds with the affinity clamp. The binding free energies evaluated by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methodology successfully ranked the ligand binding free energies, which is in agreement with the surface plasmon resonance (SPR) experiment. The further decomposition of the binding free energy revealed that electrostatic interactions, Van der Waals and hydrophobic interactions are predominant to the binding affinity difference. Our MD simulation results will provide structural and mechanistic insights for further optimization of the interactions between the affinity clamp and catenin peptides.

📜 SIMILAR VOLUMES

Species specificity of the complement in
Species specificity of the complement inhibitor compstatin investigated by all-atom molecular dynamics simulations
✍ Phanourios Tamamis; Dimitrios Morikis; Christodoulos A. Floudas; Georgios Archon 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 834 KB

## Abstract The development of compounds to regulate the activation of the complement system in non‐primate species is of profound interest because it can provide models for human diseases. The peptide compstatin inhibits protein C3 in primate mammals and is a potential therapeutic agent against un

Investigating the disorder–order transit
Investigating the disorder–order transition of calmodulin binding domain upon binding calmodulin using molecular dynamics simulation
✍ Yong Zhang; Hongwei Tan; Guangju Chen; Zongchao Jia 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 359 KB

## Abstract We have studied the conformational transition of the calmodulin binding domains (CBD) in several calmodulin‐binding kinases, in which CBD changes from the disordered state to the ordered state when binding with calmodulin (CaM). Targeted molecular dynamics simulation was used to investi

Conformational changes of the p53-bindin
Conformational changes of the p53-binding cleft of MDM2 revealed by molecular dynamics simulations
✍ L. M. Espinoza-Fonseca; José G. Trujillo-Ferrara 📂 Article 📅 2006 🏛 Wiley (John Wiley & Sons) 🌐 English ⚖ 310 KB

## Abstract Two 35‐ns molecular dynamics simulations of both ligated [mouse double minute protein 2 (MDM2^p53^)] and unligated (MDM2^apo^) structures of human MDM2 bound to the N‐terminal domain of the tumor suppressor p53 have been performed. Analysis of the dynamics revealed that the most flexibl

Conformation of the Ras-binding domain o
Conformation of the Ras-binding domain of Raf studied by molecular dynamics and free energy simulations
✍ Jun Zeng; Herbert R. Treutlein; Thomas Simonson 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 693 KB

Recognition of Ras by its downstream target Raf is mediated by a Rasrecognition region in the Ras-binding domain (RBD) of Raf. Residues 78-89 in this region occupy two different conformations in the ensemble of NMR solution structures of the RBD: a fully ␣-helical one, and one where 87-90 form a typ

The NMR structure of [Xd(C2)]4 investiga
The NMR structure of [Xd(C2)]4 investigated by molecular dynamics simulations
✍ Thérèse E. Malliavin; Karim Snoussi; Jean-Louis Leroy 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 343 KB

## Abstract The i‐motif tetrameric structure is built up from two parallel duplexes intercalated in a head‐to‐tail orientation, and held together by hemiprotonated cytosine pairs. Two topologies exist for the i‐motif structure, one with outermost 3′ extremities and the other with outermost 5′ extre