Protein Politics: How Neutral is Neutral?

IONESCU, Crina-Maria, Radka SVOBODOVÁ VAŘEKOVÁ and Jaroslav KOČA. Protein Politics: How Neutral is Neutral? In X Girona Seminar on Theoretical and Computational Chemistry for the Modeling of Biochemical Systems From Theory to Applications. 2012.

Basic information

• Original name: Protein Politics: How Neutral is Neutral?
• Authors: IONESCU, Crina-Maria, Radka SVOBODOVÁ VAŘEKOVÁ and Jaroslav KOČA.
• Edition: X Girona Seminar on Theoretical and Computational Chemistry for the Modeling of Biochemical Systems From Theory to Applications, 2012.

Other information

• Type of outcome: Presentations at conferences
• Confidentiality degree: is not subject to a state or trade secret
• Keywords in English: proteins, atomic charges
• Tags: International impact

Abstract

Proteins are long, non-neutral molecular chains with complex 3D assembly and conformational flexibility. It is thus not trivial to model the structure and behavior of proteins, due to computational complexity. Most modeling approaches completely overlook charge transfer, even though this phenomenon was found to be significant in many biomolecular interactions, and functionally linked to protein structural dynamics [1,2]. Simulations typically consider that all amino acid residues have integral total charge. However, it was recently shown that for ubiquitin [3,4] and bovine pancreatic trypsin inhibitor [5], the net total charge on many amino acid residues is not integral, and it can fluctuate during the simulation. We have set out to determine whether electron density is indeed confined to our traditional understanding of molecular fragments. In our study, we focused on amino acid residues making up protein chains, and employed Quantum Mechanical atomic charge calculation approaches to evaluate precisely how much charge can typically be transferred inside proteins and by which residues. We also attempted to find out what factors affect the amount of charge transferred, and to what degree. Ultimately, we hope to be able to conclude whether amino acid residues traditionally regarded as neutral indeed carry net zero charge, or whether it is common for them to borrow or lend charge density to neighboring residues.