Balanced Force Field ff03CMAP Improving the Dynamics Conformation Sampling of Phosphorylation Site

Abstract

Phosphorylation plays a key role in plant biology, such as the accumulation of plant cells to form the observed proteome. Statistical analysis found that many phosphorylation sites are located in disordered regions. However, current force fields are mainly trained for structural proteins, which might not have the capacity to perfectly capture the dynamic conformation of the phosphorylated proteins. Therefore, we evaluated the performance of ff03CMAP, a balanced force field between structural and disordered proteins, for the sampling of the phosphorylated proteins. The test results of 11 different phosphorylated systems, including dipeptides, disordered proteins, folded proteins, and their complex, indicate that the ff03CMAP force field can better sample the conformations of phosphorylation sites for disordered proteins and disordered regions than ff03. For the solvent model, the results strongly suggest that the ff03CMAP force field with the TIP4PD water model is the best combination for the conformer sampling. Additional tests of CHARMM36m and FB18 force fields on two phosphorylated systems suggest that the overall performance of ff03CMAP is similar to that of FB18 and better than that of CHARMM36m. These results can help other researchers to choose suitable force field and solvent models to investigate the dynamic properties of phosphorylation proteins.

Structure–function relationships in protein homorepeats

“…In the absence of extensive structural data for homorepeats, computational structural biology approaches represent an excellent alternative. Great efforts have been done in the recent years to deliver robust protein force-fields and water models to derive atomistic models of disordered proteins with the capacity to reproduce experimental data [99][100][101][102]. The refinement of these physical models to accurately simulate LCRs and homorepeats is a logical subsequent step[103*].…”

Precise Generation of Conformational Ensembles for Intrinsically Disordered Proteins via Fine-tuned Diffusion Models

“…However, MD simulation incurs high sampling costs, and ensuring thorough sampling of the ensemble is challenging. Additionally, commonly used force fields for IDPs, such as ff03CMAP 16 , ff14IDPs 17 , ESFF1 18 , still exhibit considerable errors in estimating local and global properties of IDPs during simulations 19,20 . Although we can adjust MD simulations to better align with the characteristics of IDPs using experimental data, only a few of these proteins have been experimentally characterized 21 .…”

Phosphorylation Modification Force Field FB18CMAP Improving Conformation Sampling of Phosphoproteins

“…In terms of enhancing phosphoprotein sampling, we evaluated the performance of FB18 on two folded phosphoproteins (PDB IDs: 2LKJ and 1NZS). The results indicate that FB18 erroneously unfolds the helical conformation on the phosphorylation sites within 200 ns for 2LKJ and 500 ns for 1NZS among five parallel trajectories as shown in Figure .…”