Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• essential to explain their biological functions. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. We analyze the binding interactions between GAGs of three types (heparin, desulfated heparan sulfate, and chondroitin sulfate

• be a potential mechanism of GAG particular sequence recognition by proteins. Keywords: glycosaminoglycan; molecular docking; protein–glycosaminoglycan interaction specificity; RS-REMD; umbrella sampling; Introduction Glycosaminoglycans (GAGs) are long linear periodic anionic polydisperse

• /pdb, [37]). The third complex is known to exist in two different binding poses which are experimentally well established. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. The main focus of our study is to evaluate

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• methods of enhanced sampling are introduced in literature, including: accelerated molecular dynamics [196][197], metadynamics [198][199], umbrella sampling [200] and temperature-accelerated molecular dynamics [201][202]. Accelerated molecular dynamics (aMD) simulations reduce the energy barrier of wells

• metadynamics to predict protein–ligand complexes in a reliable way. By incorporating metadynamics with induced fit methods, the predictive power of these methods can be enhanced without requiring too much computational resources [4]. The umbrella sampling technique is used to calculate free energy differences

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• (PMF), computed from MD simulations at the AM1/CHARMM/TIP3P level with umbrella sampling along a reaction coordinate defined as the difference in bond lengths from Cα to the nucleophile and nucleofuge, predicted a 44 kJ mol−1 increase ΔG‡enz in free energy in going from the enzymic reactant complex