Why protein conformers in molecular dynamics simulations differ from their   crystal structures: a thermodynamic insight

Filippo PULLARA; Mao WENZHI; Mert GÜR

Makale detayları

Why protein conformers in molecular dynamics simulations differ from their crystal structures: a thermodynamic insight

Yazarlar:

Filippo PULLARA | Mao WENZHI | Mert GÜR

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Chemistry 2019 Vol.43 Issue 2, pp.394-403

Belge Tipi:

Makale

Yayın Tarihi:

3/2019

Belge Dili:

Türkçe

Document ID (Org No.):

2000725768

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527

Özet:

 

Conformers generally deviate structurally from their starting X-ray crystal   structures early in molecular dynamics (MD) simulations. Studies have   recognized such structural differences and attempted to provide an   explanation for and justify the necessity of MD equilibrations. However, a   detailed explanation based on fundamental physics and validation on a large   ensemble of protein structures is still missing. Here we provide the first   thermodynamic insights into the radically different thermodynamic conditions   of crystallization solutions and conventional MD simulations.   Crystallization solution conditions can lead to nonphysiologically high ion   concentrations, low temperatures, and crystal packing with strong specific   protein--protein interactions, not present under physiological conditions.   These differences affect protein conformations and functions, and MD   structures equilibrated or simulated under physiological conditions are   usually expected to differ from their X-ray structures at a local scale,   while the global fold is usually maintained. To quantify this property, we   performed conventional MD simulations for over 70 different proteins   spanning a broad range of molecular size and structural and functional   families. Our analysis shows that crystal structures are good starting   points; however, they do not represent structures in their physiological   environment. This fact has to be taken into consideration when computational   methods dependent on atomic coordinates, such as substrate/ligand docking,   are used to guide experimental analyses.

Makale detayları

Why protein conformers in molecular dynamics simulations differ from their crystal structures: a thermodynamic insight

Yazarlar: Filippo PULLARA | Mao WENZHI | Mert GÜR

Yayıncı: TUBITAK

Dergi: Turkish Journal of Chemistry 2019 Vol.43 Issue 2, pp.394-403

Belge Tipi: Makale

Yayın Tarihi: 3/2019

Belge Dili: Türkçe

Document ID (Org No.): 2000725768

Sıklık: İki Aylık

eISSN: 1303-6130

pISSN: 1300-0527

Sayı

Yazarlar:

Filippo PULLARA | Mao WENZHI | Mert GÜR

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Chemistry 2019 Vol.43 Issue 2, pp.394-403

Belge Tipi:

Makale

Yayın Tarihi:

3/2019

Belge Dili:

Türkçe

Document ID (Org No.):

2000725768

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527