Biomaterial Database

Enthalpy-Entropy Compensation upon Molecular Conformational Changes. 2015

Mazen Ahmad, and Volkhard Helms, and Thomas Lengauer, and Olga V Kalinina

Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics , Campus E1 4, 66123 Saarbrücken, Germany.

The change in free energy is the dominant factor in all chemical processes; it usually encompasses enthalpy-entropy compensation (EEC). Here, we use the free energy perturbation formalism to show that EEC is influenced by the molecular conformational changes (CCs) of the entire system comprising the solute and by the already known solvent reorganization. The internal changes of enthalpy and the entropy due to CCs upon modifying the interactions (perturbation) cancel each other exactly. The CCs influence the dissipation of the modified interactions and their contributions to the free energy. Using molecular simulations, we show that, for solvation of six different HIV-1 protease inhibitors, CCs in the solute cause EEC as large as 10-30 kcal/mol. Moreover, the EEC due to CCs in HIV-1 protease is shown to vary significantly upon modifying its bound ligand. These findings have important implications for understanding of EEC phenomena and for interpretation of thermodynamic measurements.

UI	MeSH Term	Description	Entries
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D015497	HIV-1	The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.	Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D016333	HIV Protease	Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.	HIV Proteinase,HTLV-III Protease,p16 pol gene product, HIV,p16 protease, HIV,HIV p16 protease,HTLV III Protease,Protease, HIV,Protease, HTLV-III
D017320	HIV Protease Inhibitors	Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.	HIV Protease Inhibitor,Inhibitor, HIV Protease,Inhibitors, HIV Protease,Protease Inhibitor, HIV,Protease Inhibitors, HIV
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D019277	Entropy	The measure of that part of the heat or energy of a system which is not available to perform work. Entropy increases in all natural (spontaneous and irreversible) processes. (From Dorland, 28th ed)	Entropies