,
Isabella Daidone *, Massimiliano Anselmi *,
Beatrice Vallone 
,
Maurizio Brunori
and Alfredo Di
Nola *
Cecilia Bossa *, Andrea
Amadei ,
Isabella Daidone *, Massimiliano Anselmi *,
Beatrice Vallone ,
Maurizio Brunori
and Alfredo Di
Nola *
* Dipartimento
di
Chimica, University of Rome "La Sapienza", Rome, Italy;
Dipartimento
di
Scienze e Tecnologie Chimiche, University of Rome "Tor Vergata",
Rome, Italy; and
Dipartimento
di
Scienze Biochimiche, University of Rome "La Sapienza",
Rome, Italy
Correspondence: Address reprint requests to Cecilia Bossa, University of Rome "La Sapienza", Piazzale Aldo Moro 5, Rome 00185, Italy. Fax: 39-06-490324; E-mail: cebossa@caspur.it.
The results of extended (80-ns) molecular dynamics simulations of wild-type and YQR triple mutant of sperm whale deoxy myoglobin in water are reported and compared with the results of the simulation of the intermediate(s) obtained by photodissociation of CO in the wild-type protein. The opening/closure of pathways between preexistent cavities is different in the three systems. For the photodissociated state, we previously reported a clear-cut correlation between the opening probability and the presence of the photolyzed CO in the proximity of the passage; here we show that in wild-type deoxy myoglobin, opening is almost random. In wild-type deoxy myoglobin, the passage between the distal pocket and the solvent is strictly correlated to the presence/absence of a water molecule that simultaneously interacts with the distal histidine side chain and the heme iron; conversely, in the photodissociated myoglobin, the connection with the bulk solvent is always open when CO is in the vicinity of the A pyrrole ring. In YQR deoxy myoglobin, the mutated Gln(E7)64 is stably H-bonded with the mutated Tyr(B10)29. The essential dynamics analysis unveils a different behavior for the three systems. The motion amplitude is progressively restricted in going from wild-type to YQR deoxy myoglobin and to wild-type myoglobin photoproduct. In all cases, the principal motions involve mainly the same regions, but their directions are different. Analysis of the dynamics of the preexisting cavities indicates large fluctuations and frequent connections with the solvent, in agreement with the earlier hypothesis that some of the ligand may escape from the protein through these pathways.