Influence of external force on properties and reactivity of disulfide bonds.

نویسندگان

  • Maria Francesca Iozzi
  • Trygve Helgaker
  • Einar Uggerud
چکیده

The mechanochemistry of the disulfide bridge--that is, the influence of an externally applied force on the reactivity of the sulfur-sulfur bond--is investigated by unrestricted Kohn-Sham theory. Specifically, we apply the COGEF (constrained geometry simulates external force) approach to characterize the mechanochemistry of the disulfide bond in three different chemical environments: dimethyl disulfide, cystine, and a 102-atom model of the I27 domain in the titin protein. Furthermore, the mechanism of the thiol-disulfide reduction reaction under the effect of an external force is investigated by considering the COGEF potential for the adduct and transition-state clusters. With the unrestricted Becke-three-parameter-Lee-Yang-Parr (UB3LYP) exchange-correlation functional in the 6-311++G(3df,3pd) orbital basis, the rupture force of dimethyl disulfide is 3.8 nN at a disulfide bond elongation of 35 pm. The interaction with neighboring groups and the effect of conformational rigidity of the protein environment have little influence on the mechanochemical characteristics. Upon stretching, we make the following observations: the diradical character of the disulfide bridge increases; the energy difference between the singlet ground state and low-lying triplet state decreases; and the disulfide reduction is promoted by an external force in the range 0.1-0.4 nN. Our model of the interplay between force and reaction mechanism is in qualitative agreement with experimental observations.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The influence of disulfide bonds on the mechanical stability of proteins is context dependent.

Disulfide bonds play a crucial role in proteins, modulating their stability and constraining their conformational dynamics. A particularly important case is that of proteins that need to withstand forces arising from their normal biological function and that are often disulfide bonded. However, the influence of disulfides on the overall mechanical stability of proteins is poorly understood. Her...

متن کامل

Quantum chemistry studies on reactivity of the 2-Amino-3-(3,4-Dihydroxyphenyl)Propanoic Aciddrug linked to to C60

In this research at the first 2-amino-3-(3,4-dihydroxyphenyl) propanoic aciddrug  drug and its fullerene derivative were optimized. NBO calculations and NMR for the complexes were carried out at the B3LYP/6-31G*quantum chemistry level. Different parameters such as energy levels, the amount of Chemical Shift in different atoms, the amount of HOMO/LUMO, chemical potential (µ ), chemical hardness ...

متن کامل

Investigation of Fullerene effect on reactivity of 2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid with NMR parameters

In this research at the first 2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid  drug and its fullerene derivative were optimized. NMR calculations for the complexes were carried out at the B3LYP/6-31G*quantum chemistry level. Different parameters such as energy levels, the amount of Chemical Shift in different atoms, the amount of HOMO/LUMO, chemical potential (µ ), chemical hardness (η)...

متن کامل

Tailoring protein nanomechanics with chemical reactivity

The nanomechanical properties of elastomeric proteins determine the elasticity of a variety of tissues. A widespread natural tactic to regulate protein extensibility lies in the presence of covalent disulfide bonds, which significantly enhance protein stiffness. The prevalent in vivo strategy to form disulfide bonds requires the presence of dedicated enzymes. Here we propose an alternative chem...

متن کامل

Force-activated reactivity switch in a bimolecular chemical reaction.

The effect of mechanical force on the free-energy surface that governs a chemical reaction is largely unknown. The combination of protein engineering with single-molecule force-clamp spectroscopy allows us to study the influence of mechanical force on the rate at which a protein disulfide bond is reduced by nucleophiles in a bimolecular substitution reaction (S(N)2). We found that cleavage of a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The journal of physical chemistry. A

دوره 115 11  شماره 

صفحات  -

تاریخ انتشار 2011