Related Experiment Video
Updated: Jun 16, 2026
07:33
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Conformational dynamics and ligand binding in the multi-domain protein PDC109
Hyun Jin Kim1, Moo Young Choi, Hyung J Kim
1Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
Plos One
|February 23, 2010
Summary
Phosphorylcholine (PhC) binding to the bull protein PDC109 influences the orientation of its fibronectin type II (Fn2) domains. Molecular dynamics simulations reveal how PhC binding affects protein flexibility and domain interactions.
Area of Science:
- Structural biology
- Molecular dynamics simulations
- Protein-ligand interactions
Background:
- PDC109 is a multi-domain protein crucial for bull sperm-oviduct interactions.
- It binds to phosphorylcholines (PhCs), key components of sperm cell membranes.
Purpose of the Study:
- To investigate the dynamic effects of PhC binding on PDC109's structure and domain orientation.
- To elucidate the energetics and mechanisms of PDC109-PhC interactions using computational methods.
Main Methods:
- Long timescale explicit solvent molecular dynamics (MD) simulations of PDC109 with and without PhC.
- Calculation of potential of mean force to estimate the association constant.
- Principal component analysis (PCA) and normal mode analysis (NMA) to study domain motions.
Main Results:
- PhC binding significantly influences the relative orientation of PDC109's two Fn2 domains.
- Simulations show domain reorientation driven by linker deformation in the absence of tight PhC binding.
- Estimated association constant (28 M(-1)) aligns with experimental findings.
- PCA and NMA effectively capture the differences in domain motion between bound and unbound states.
Conclusions:
- MD simulations provide insights into the energetics of ligand-domain interactions and their impact on protein dynamics.
- The study clarifies how PhC binding modulates the conformational landscape of the multi-domain protein PDC109.
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
02:40Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
02:40Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...