Thermal stability of single‐domain antibodies estimated by molecular dynamics simulations
| Autor: | Narutoshi Kamiya, Benson Ma, Gert-Jan Bekker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Work (thermodynamics)
Hot Temperature Q value Full‐Length Papers point mutations Biochemistry Instability melting temperature thermal stability single‐domain antibody 03 medical and health sciences Molecular dynamics Full‐Length Paper Thermal stability Single domain Molecular Biology 030304 developmental biology 0303 health sciences Chemistry Protein Stability 030302 biochemistry & molecular biology Single-Domain Antibodies Single-domain antibody molecular dynamics simulation Chemical physics Biosensor |
| Zdroj: | Protein Science : A Publication of the Protein Society |
| ISSN: | 1469-896X 0961-8368 |
| Popis: | Single‐domain antibodies (sdAbs) function like regular antibodies, however, consist of only one domain. Because of their low molecular weight, sdAbs have advantages with respect to production and delivery to their targets and for applications such as antibody drugs and biosensors. Thus, sdAbs with high thermal stability are required. In this work, we chose seven sdAbs, which have a wide range of melting temperature (T m) values and known structures. We applied molecular dynamics (MD) simulations to estimate their relative stability and compared them with the experimental data. High‐temperature MD simulations at 400 K and 500 K were executed with simulations at 300 K as a control. The fraction of native atomic contacts, Q, measured for the 400 K simulations showed a fairly good correlation with the T m values. Interestingly, when the residues were classified by their hydrophobicity and size, the Q values of hydrophilic residues exhibited an even better correlation, suggesting that stabilization is correlated with favorable interactions of hydrophilic residues. Measuring the Q value on a per‐residue level enabled us to identify residues that contribute significantly to the instability and thus demonstrating how our analysis can be used in a mutant case study. |
| Databáze: | OpenAIRE |
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