[Paper Review] Chain-Growth Simulations of Lattice-Peptide Adsorption to Attractive Substrates

Michaël Bachmann, Wolfhard Janke|ArXiv.org|Oct 23, 2007

Supramolecular Self-Assembly in Materials3 citations

TL;DR

This study employs a contact-density chain-growth algorithm to simulate a 103-residue lattice peptide on attractive substrates, enabling systematic reweighting to all temperatures and solvent qualities. The key contribution is a detailed solubility-temperature pseudo-phase diagram revealing rich, substrate-specific conformational transitions, including first-order-like adsorption/desorption and second-order-like compact-to-expanded transitions, with distinct subphases in adsorbed states.

ABSTRACT

Based on a newly developed contact-density chain-growth algorithm, we have simulated a nongrafted peptide in the vicinity of different attractive substrates. We analyzed the specificity of the peptide adsorption by focussing on the conformational transitions the peptide experiences in the binding/unbinding processes. In a single simulation run, we obtained the contact density, i.e., the distribution of intrinsic monomer-monomer contacts and monomer-substrate nearest-neighbor contacts. This allows a systematic reweighting to all values of external control parameters such as temperature and solvent quality after the simulation. The main result is the complete solubility-temperature pseudo-phase diagram which is based on the corresponding specific-heat profile. We find a surprisingly rich structure of pseudo-phases that can roughly be classified into compact and expanded conformations in both regimes, adsorption and desorption. Furthermore, underlying subphases were identified, which, in particular, appear noticeably in the compact pseudo-phases.

Motivation & Objective

• To investigate the specificity of peptide adsorption to substrates with varying affinities for hydrophobic and polar residues.
• To understand how solvent quality and temperature influence conformational transitions in non-grafted peptides near adsorbing surfaces.
• To map the complete pseudo-phase diagram of conformational states using a single simulation run with reweighting capabilities.
• To identify and characterize subphases within adsorbed and desorbed regimes, particularly in compact and expanded conformations.
• To explore the thermodynamic and structural basis for peptide binding, refolding, and desorption under varying environmental conditions.

Proposed method

• A contact-density chain-growth algorithm is used to sample all macro-states defined by monomer-substrate contacts ($n_s$) and hydrophobic contacts ($n_{\rm HH}$) in a single simulation run.
• The method enables systematic reweighting to all values of temperature ($T$) and solvent quality ($s$), bypassing slow-downs in conventional Monte Carlo methods.
• The energy of the system is defined as $E_s(n_s, n_{\rm HH}) = -n_s - s n_{\rm HH}$, with $s$ controlling solvent quality.
• The system is confined in a cavity with an attractive substrate and a neutral wall at $z_w = 200$ to regularize unbound conformations.
• Free energy minima are identified by minimizing $F_{T,s}(n_s^{(0)}, n_{\rm HH}^{(0)})$, and the resulting pseudo-phase diagram is mapped across $T \in [0,10]$ and $s \in [-2,10]$.
• Conformational transitions are analyzed via specific-heat profiles and contact density distributions, with transitions classified as first- or second-order-like based on discontinuities in contact numbers.

Experimental results

Research questions

• RQ1 How does the solvent quality ($s$) influence the stability and structure of adsorbed peptide conformations on different substrates?
• RQ2 What are the nature and characteristics of conformational transitions between adsorbed and desorbed states?
• RQ3 Are there distinct subphases within the adsorbed regime, and how do they depend on substrate specificity and temperature?
• RQ4 How do hydrophobic and polar residue interactions compete with substrate binding in determining the peptide's conformational landscape?
• RQ5 What is the role of entropy and enthalpy in driving transitions from single-layer to multi-layer and finally to desorbed, expanded conformations?

Key findings

• The pseudo-phase diagram reveals a rich structure of conformational states, including compact (AC1, AC2, AG) and expanded (AE, DE) phases, with distinct transitions between them.
• A first-order-like transition occurs at $T \approx 0.35$ for $s = 2.5$, marked by the formation of a second adsorbed layer and a sharp change in contact numbers.
• The transition from AC2 to AG and then to AE is second-order-like, with gradual changes in hydrophobic and substrate contact numbers, indicating smooth conformational evolution.
• The unbinding transition near $T \approx 2.14$ is also first-order-like, with coexistence of adsorbed and desorbed conformations and a dramatic loss of substrate contacts.
• Subphases are particularly prominent in compact pseudo-phases, especially in the AC1 and AC2 regimes, indicating complex interplay between surface binding and hydrophobic core formation.
• The method successfully captures the full thermodynamic landscape, including the ground state with 56 hydrophobic contacts and a degeneracy of $10^{16}$, despite the model's coarse-grained nature.