m-values (protein transfer free energy) calculator

mvalue(; model=MoeserHorinek, cosolvent="urea", pdbname, sasas, type=1)

Calculates the m-value (transfer free energy of a protein in 1M solution) using the Tanford transfer model, as implemented by Moeser and Horinek [1] or by Auton and Bolen [2,3].

Arguments

• model: The model to be used. Must be MoeserHorinek or AutonBolen. MoeserHorinek is only implemented for cosolvent="urea", and should be more precise in that case. Other solvents are available for AutonBolen.

• cosolvent::String: One of "Betaine", "Proline", "Sarcosine", "Sorbitol", "Sucrose", "Tmao", "tmao", "TMAO", "urea", "Urea", "UREA", "UreaApp", "UreaMH"

• pdbname::AbstractString: Path to the PDB file of the protein structure.

• sasas::Dict{String, Dict{Symbol, Float64}}: A dictionary containing the change in solvent accessible surface area (SASA) upon denaturation for each amino acid type. This data can be obtained from the m-value server or calculated using GROMACS:

  • The output of the server can be parsed using the parse_mvalue_server_sasa function defined in this module.
  • Alternatively, the SASA values can be calculated using GROMACS with the gmx_sasa function defined in this module.

• type::Int: Specifies which SASA value to use from the provided data, because the server provides minimum, average, and maximum values, according to different denatured models for the protein. The recommended value is 2 for comparison with experimental data. Normally, GROMACS calculations will provide a single value, so type=1 should be used in that case.

Returns

A named tuple with the following fields:

• tot: Total transfer free energy (kcal/mol).
• bb: Contribution from the backbone (kcal/mol).
• sc: Contribution from the side chains (kcal/mol).
• restype: A dictionary with the transfer free energy contributions per residue type (kcal/mol).

Each entry in the dictionary is a named tuple with bb and sc fields representing the backbone and side chain contributions, respectively.

Example calls

# Using SASA values from the m-value server
sasas_from_server=parse_mvalue_server_sasa(server_output)
mvalue(; model=MoeserHorinek, cosolvent="urea", pdbname="protein.pdb", sasas=sasas_from_server, type=2)

# Using SASA values calculated with GROMACS
sasas_gmx=gmx_sasa(native_pdb="native.pdb", desnat_pdb="desnat.pdb")
mvalue(; model=AutonBolen, cosolvent="TMAO", pdbname="protein.pdb", sasas=sasas_gmx, type=1)

References

1. https://doi.org/10.1021/acs.jpcb.7b02138
2. https://doi.org/10.1016/s0076-6879(07)28023-1
3. https://www.pnas.org/doi/10.1073/pnas.0706251104

gmx_sasa(; native_pdb::AbstractString, desnat_pdb::AbstractString)

Calculates the change in solvent accessible surface area (SASA) upon denaturation for each amino acid type using GROMACS. Returns a dictionary that can be directly used as input to the mvalue function.

Arguments

• native_pdb::AbstractString: Path to the PDB file of the native protein structure.
• desnat_pdb::AbstractString: Path to the PDB file of the denatured protein structure.

Returns

A dictionary where each key is an amino acid three-letter code (e.g., "ALA", "PHE"), and the value is another dictionary with two keys: :sc for side chain SASA values and :bb for backbone SASA values. Each of these keys maps to a tuple containing a single Float64 value representing the change in SASA upon denaturation in Ų.

parse_mvalue_server_sasa(string::AbstractString)

Parses the SASA output from the m-value calculator server (http://best.bio.jhu.edu/mvalue/), into a dictionary that can be directly used as input to the mvalue function.

The input string should contain lines formatted as follows, and correspond to the SASA values for each amino acid type:

sasa_from_server = """
ALA 	8 	 (    11.1)     79.1 [   147.1] | (   -13.0)     51.4 [   115.8] 
PHE 	3 	 (   166.9)    197.1 [   230.2] | (    29.4)     56.4 [    83.4] 
LEU 	7 	 (   475.2)    532.2 [   589.3] | (    89.3)    145.3 [   201.3] 
...
LYS 	6 	 (   171.5)    220.4 [   269.3] | (    -4.5)     42.0 [    88.5] 
ARG 	1 	 (   110.2)    124.4 [   138.6] | (    17.1)     25.0 [    33.0] 
CYS 	0 	 (     0.0)      0.0 [     0.0] | (     0.0)      0.0 [     0.0] 
"""

This data can be found in the output of the server, under the title "Sidechain and Backbone changes in Accessible Surface Area".

The function returns a dictionary where each key is an amino acid three-letter code (e.g., "ALA", "PHE"), and the value is another dictionary with two keys: :sc for side chain SASA values and :bb for backbone SASA values. Each of these keys maps to a tuple containing three Float64 values representing the minimum, average, and maximum SASA values in Ų.