Contents lists available at ScienceDirect Chinese Journal of Physics journal homepage: www.elsevier.com/locate/cjph Conformational stability of the tetrameric de novo designed hexcoil-Ala helical bundle Kadir Demir a, ⁎ , Hakan Alıcı a , Fatih Yaşar b a Bülent Ecevit University, Department of Physics, Zonguldak 67100, Turkey b Hacettepe University, Department of Physics Engineering, Ankara 06800, Turkey ARTICLE INFO Keywords: Molecular dynamics Simulation Self-assembly Stability Protein Peptide ABSTRACT We have performed molecular dynamics method to investigate the conformational stability of the homotetramer form of HexCoil-Ala (PDB Code 3S0R). The previous experiments showed that the chains tend to form tetramer structures. The system was simulated in explicit water model at several temperatures by using isobaric-isothermal ensemble to better understand the behaviour of each monomer and its tetramer form. It was observed that central residues of each monomer have highly helical percentages in comparison with the termini residues. As the temperature increased, these percentages decreased, and bend-like configurations came into being due to the fact that the C-and N-terminals of the monomer were getting closer. When free energy landscapes of HexCoil-Ala were calculated by using the distance between Leu-Zipper and Ala-Coil interface, it was seen that the assemblies of monomers were very strong. What's more, the average values obtained from them were very close to the native case between 300 K and 350 K. It was also observed that the direct salt bridge forming between the residues E8 with R25 in the other chains plays a significant role for keeping tetramer structure. Consequently, our results are in better agreement with the results of experimental observations. 1. Introduction In cells and living organisms, proteins are responsible for stability, mobility, catalysis, recognition, pathogen clearing, signalling, ordering and shaping. These biological functions of proteins depend on their conformational shapes and folding mechanisms. There is, therefore, a growing interest in the design of protein to find out novel functionalities unavailable in nature [1,2]. These designed structures bring a lot of advantages in comparison with native proteins; for instance, conformational stability, well-folded secondary structure and self-assembly [3,4]. The ability to manipulate these functions of the proteins has particularly led to a possible design of new proteins bearing a biological value [5,6]. In recent years, thanks to computationally designed proteins, such impressive fields of application as biotechnology and drug discovery (cancer [7–10], Alzheimer's [11,12] and human immunodeficiency virus drugs [13–15], antibody therapeutics [16–20], novel biocatalyst [21–29] and self-assembling nanomaterials [30–32]) have been demon- strated. The functional proteins can be either developed from scratch, known as de novo design technique or by modification of structural motifs pre-existing in the repertoire of nature. Symmetry is one of the commonly used procedures and facilitates the design process during the design of de novo and modified structures. The importance of the symmetries, like screw symmetry in β-strands and α- helices and quasi-symmetrical arrangements occurring in proteins assemblies, is disputable for protein structures. In addition, such https://doi.org/10.1016/j.cjph.2017.12.004 Received 11 August 2017; Received in revised form 1 December 2017; Accepted 6 December 2017 ⁎ Corresponding author. E-mail address: kadirdemir@beun.edu.tr (K. Demir). Chinese Journal of Physics 56 (2018) 46–57 Available online 07 December 2017 0577-9073/ © 2017 The Physical Society of the Republic of China (Taiwan). Published by Elsevier B.V. All rights reserved. T